4,490 results on '"Immune Suppression"'
Search Results
2. Mobile Video Directly Observed Therapy (DOT) for Immunosuppression Medication Adherence in Adolescent Heart Transplant Recipients
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emocha Mobile Health, Inc. and National Heart, Lung, and Blood Institute (NHLBI)
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- 2024
3. Intravenous lipopolysaccharide challenge in early- versus mid-lactation dairy cattle. I: The immune and inflammatory responses.
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Opgenorth, J., Mayorga, E.J., Abeyta, M.A., Goetz, B.M., Rodriguez-Jimenez, S., Freestone, A.D., McGill, J.L., and Baumgard, L.H.
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HAPTOGLOBINS , *NEUTROPHILS , *DAIRY cattle , *MACROPHAGE inflammatory proteins , *INFLAMMATION , *IMMUNE response , *DAIRY cattle behavior , *FACTORIAL experiment designs , *LIPOPOLYSACCHARIDES - Abstract
The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Cows in early lactation (EL) are purportedly immune suppressed, which renders them more susceptible to disease. Thus, the study objective was to compare key biomarkers of immune activation from i.v. LPS between EL and mid-lactation (ML) cows. Multiparous EL (20 ± 2 DIM; n = 11) and ML (131 ± 31 DIM; n = 12) cows were enrolled in a 2 × 2 factorial design and assigned to 1 of 2 treatments by lactation stage (LS): (1) EL (EL-LPS; n = 6) or ML (ML-LPS; n = 6) cows administered a single LPS bolus from Escherichia coli O55:B5 (0.09 µg/kg of BW), or (2) pair-fed (PF) EL (EL-PF; n = 5) or ML (ML-PF; n = 6) cows administered i.v. saline. After LPS administration, cows were intensely evaluated for 3 d to analyze their response and recovery to LPS. Rectal temperature increased in LPS relative to PF cows (1.1°C in the first 9 h), and the response was more severe in EL-LPS relative to ML-LPS cows (2.3 vs. 1.3°C increase at 4 h post-LPS; respectively). Respiration rate increased only in EL-LPS cows (47% relative to ML-LPS in the first hour post-LPS). Circulating tumor necrosis factor-α, IL-6, monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, and IFN-γ-inducible protein-10 increased within the first 6 h after LPS and these changes were exacerbated in EL-LPS relative to ML-LPS cows (6.3-fold, 4.8-fold, 57%, 93%, 10%, and 61%, respectively). All cows administered LPS had decreased circulating iCa relative to PF cows (34% at the 6 h nadir), but the hypocalcemia was more severe in EL-LPS than ML-LPS cows (14% at 6 h nadir). In response to LPS, neutrophils decreased regardless of LS, then increased into neutrophilia by 24 h in all LPS relative to PF cows (2-fold); however, the neutrophilic phase was augmented in EL- compared with ML-LPS cows (63% from 24 to 72 h). Lymphocytes and monocytes rapidly decreased then gradually returned to baseline in LPS cows regardless of LS; however, monocytes were increased (57%) at 72 h in EL-LPS relative to ML-LPS cows. Platelets were reduced (46%) in LPS relative to PF cows throughout the 3-d following LPS, and from 24 to 48 h, platelets were further decreased (41%) in EL-LPS compared with ML-LPS. During the 3-d following LPS, serum amyloid A (SAA), LPS-binding protein (LBP), and haptoglobin (Hp) increased in LPS compared with PF groups (9-fold, 72%, and 153-fold, respectively), and the LBP and Hp responses were more exaggerated in EL-LPS than ML-LPS cows (85 and 79%, respectively) whereas the SAA response did not differ by LS. Thus, our data indicates that EL immune function does not appear "suppressed," and in fact many aspects of the immune response are seemingly functionally robust. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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4. Ameliorative effects of Sargassum kjellmanianum on hexavalent chromium-induced growth inhibition, immune suppression, and oxidative stress in yellow catfish.
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Shi, Qingchao, Hu, Peng, Wen, Zhengyong, Wang, Jun, and Zou, Yuanchao
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Chromium (Cr) pollution is a critical environmental concern posing a considerable danger to the food safety of aquatic products and health of aquatic animals. Developing a reliable and effective strategy for reducing the adverse effects of Cr on aquatic organisms is of great importance. The objective of this study was to evaluate the role of the brown alga Sargassum kjellmanianum in reducing chronic toxicity induced by hexavalent Cr (Cr6+) in yellow catfish, Pelteobagrus fulvidraco. A total of 360 healthy fish were exposed to Cr6+ (3.24 mg L-1) and S.kjellmanianum (5 % in diet), individually or in combination for 28-days. The results revealed that Cr6+ exposure significantly decreased growth performance of fish, and serum immune parameters [total protein and albumin levels, acid phosphatase, alkaline phosphatase, and lysozyme activities]. Also, it significantly increased serum aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglyceride levels and muscle Cr concentration. Additionally, significant reduction in serum total antioxidant capacity, superoxide dismutase, and catalase activities as well as marked increments of malondialdehyde were observed in Cr6+-exposed fish compared to the control group. Importantly, SK supplementation could overcome the negative impacts of Cr6+ and normalise the examined parameters nearly to the control values. In conclusion, dietary S.kjellmanianum supplementation could protect P.fulvidraco against the toxic effects of Cr6+, and therefore, may serve as a beneficial feed additive for application in the aquaculture industry. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Inflammation is a critical factor for successful regeneration of the adult zebrafish retina in response to diffuse light lesion.
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Bludau, Oliver, Weber, Anke, Bosak, Viktoria, Kuscha, Veronika, Dietrich, Kristin, Hans, Stefan, and Brand, Michael
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REGENERATION (Biology) ,NERVOUS system regeneration ,RETINA ,BRACHYDANIO ,RETINAL injuries ,ADULTS ,CD14 antigen - Abstract
Inflammation can lead to persistent and irreversible loss of retinal neurons and photoreceptors in mammalian vertebrates. In contrast, in the adult zebrafish brain, acute neural inflammation is both necessary and sufficient to stimulate regeneration of neurons. Here, we report on the critical, positive role of the immune system to support retina regeneration in adult zebrafish. After sterile ablation of photoreceptors by phototoxicity, we find rapid response of immune cells, especially monocytes/microglia and neutrophils, which returns to homeostatic levels within 14 days post lesion. Pharmacological or genetic impairment of the immune system results in a reduced Müller glia stem cell response, seen as decreased reactive proliferation, and a strikingly reduced number of regenerated cells from them, including photoreceptors. Conversely, injection of the immune stimulators flagellin, zymosan, or M-CSF into the vitreous of the eye, leads to a robust proliferation response and the upregulation of regeneration-associated marker genes in Müller glia. Our results suggest that neuroinflammation is a necessary and sufficient driver for retinal regeneration in the adult zebrafish retina. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Targeting CSF1R in myeloid-derived suppressor cells: insights into its immunomodulatory functions in colorectal cancer and therapeutic implications.
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Tong, Xin, Qiao, Shifeng, Dong, Zhe, Zhao, Xiaohui, Du, Xiaxia, and Niu, Wei
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MYELOID-derived suppressor cells , *COLORECTAL cancer , *JAK-STAT pathway , *IMMUNOSUPPRESSION , *GENE expression - Abstract
Objective: This study aimed to investigate the critical role of MDSCs in CRC immune suppression, focusing on the CSF1R and JAK/STAT3 signaling axis. Additionally, it assessed the therapeutic efficacy of LNCs@CSF1R siRNA and anti-PD-1 in combination. Methods: Single-cell transcriptome sequencing data from CRC and adjacent normal tissues identified MDSC-related differentially expressed genes. RNA-seq analysis comprehensively profiled MDSC gene expression in murine CRC tumors. LNCs@CSF1R siRNA nanocarriers effectively targeted and inhibited CSF1R. Flow cytometry quantified changes in MDSC surface markers post-CSF1R inhibition. RNA-seq and pathway enrichment analyses revealed the impact of CSF1R on MDSC metabolism and signaling. The effect of CSF1R inhibition on the JAK/STAT3 signaling axis was validated using Colivelin and metabolic assessments. Glucose and fatty acid uptake were measured via fluorescence-based flow cytometry. The efficacy of LNCs@CSF1R siRNA and anti-PD-1, alone and in combination, was evaluated in a murine CRC model with extensive tumor section analyses. Results: CSF1R played a significant role in MDSC-mediated immune suppression. LNCs@CSF1R siRNA nanocarriers effectively targeted MDSCs and inhibited CSF1R. CSF1R regulated MDSC fatty acid metabolism and immune suppression through the JAK/STAT3 signaling axis. Inhibition of CSF1R reduced STAT3 activation and target gene expression, which was rescued by Colivelin. Combined treatment with LNCs@CSF1R siRNA and anti-PD-1 significantly slowed tumor growth and reduced MDSC abundance within CRC tumors. Conclusion: CSF1R via the JAK/STAT3 axis critically regulates MDSCs, particularly in fatty acid metabolism and immune suppression. Combined therapy with LNCs@CSF1R siRNA and anti-PD-1 enhances therapeutic efficacy in a murine CRC model, providing a strong foundation for future clinical applications. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Role of FoxP3+ Regulatory T Cells in Modulating Immune Responses to Adeno-Associated Virus Gene Therapy.
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Muñoz-Melero, Maite and Biswas, Moanaro
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REGULATORY T cells , *T cells , *GENE therapy , *GENETIC vectors , *ADENO-associated virus , *IMMUNE response , *CYTOTOXIC T cells - Abstract
Adeno-associated virus (AAV) gene therapy is making rapid strides owing to its wide range of therapeutic applications. However, development of serious immune responses to the capsid antigen or the therapeutic transgene product hinders its full clinical impact. Immune suppressive (IS) drug treatments have been used in various clinical trials to prevent the deleterious effects of cytotoxic T cells to the viral vector or transgene, although there is no consensus on the best treatment regimen, dosage, or schedule. Regulatory T cells (Tregs) are crucial for maintaining tolerance against self or nonself antigens. Of importance, Tregs also play an important role in dampening immune responses to AAV gene therapy, including tolerance induction to the transgene product. Approaches to harness the tolerogenic effect of Tregs include the use of selective IS drugs that expand existing Tregs, and skew activated conventional T cells into antigen-specific peripherally induced Tregs. In addition, Tregs can be expanded ex vivo and delivered as cellular therapy. Furthermore, receptor engineering can be used to increase the potency and specificity of Tregs allowing for suppression at lower doses and reducing the risk of disrupting protective immunity. Because immune-mediated toxicities to AAV vectors are a concern in the clinic, strategies that can enhance or preserve Treg function should be considered to improve both the safety and efficacy of AAV gene therapy. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Inactivated Aeromonas salmonicida impairs adaptive immunity in lumpfish (Cyclopterus lumpus).
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Chakraborty, Setu, Gnanagobal, Hajarooba, Hossain, Ahmed, Cao, Trung, Vasquez, Ignacio, Boyce, Danny, and Santander, Javier
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AEROMONAS salmonicida , *IMMUNITY , *VACCINE approval , *VACCINE effectiveness , *MEMBRANE proteins - Abstract
Aeromonas salmonicida, a widely distributed aquatic pathogen causing furunculosis in fish, exhibits varied virulence, posing challenges in infectious disease and immunity studies, notably in vaccine efficacy assessment. Lumpfish (Cyclopterus lumpus) has become a valuable model for marine pathogenesis studies. This study evaluated several antigen preparations against A. salmonicida J223, a hypervirulent strain of teleost fish, including lumpfish. The potential immune protective effect of A. salmonicida bacterins in the presence and absence of the A‐layer and extracellular products was tested in lumpfish. Also, we evaluated the impact of A. salmonicida outer membrane proteins (OMPs) and iron‐regulated outer membrane proteins (IROMPs) on lumpfish immunity. The immunized lumpfish were intraperitoneally (i.p.) challenged with 104A. salmonicida cells/dose at 8 weeks‐post immunization (wpi). Immunized and non‐immunized fish died within 2 weeks post‐challenge. Our analyses showed that immunization with A. salmonicida J223 bacterins and antigen preparations did not increase IgM titres. In addition, adaptive immunity biomarker genes (e.g., igm, mhc‐ii and cd4) were down‐regulated. These findings suggest that A. salmonicida J223 antigen preparations hinder lumpfish immunity. Notably, many fish vaccines are bacterin‐based, often lacking efficacy evaluation. This study offers crucial insights for finfish vaccine approval and regulations. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Severe thermal and major traumatic injury results in elevated plasma concentrations of total heme that are associated with poor clinical outcomes and systemic immune suppression.
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Tullie, Sebastian, Nicholson, Thomas, Bishop, Jonathan R. B., McGee, Kirsty C., Asiri, Ali, Sullivan, Jack, Yung-Yi Chen, Sardeli, Amanda V., Belli, Antonio, Harrison, Paul, Moiemen, Naiem S., Lord, Janet M., and Hazeldine, Jon
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HAPTOGLOBINS ,IMMUNOSUPPRESSION ,HEME ,MONONUCLEAR leukocytes ,ERYTHROCYTES ,TREATMENT effectiveness - Abstract
Background: Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from injured muscle and lysed red blood cells, heme is a damage associated molecular pattern with potent immune modulatory properties. Here, we measured plasma concentrations of total heme in over 200 traumatic and thermally-injured patients in order to examine its relationship with clinical outcomes and post-injury immune suppression. Methods: Blood samples were collected from 98 burns (=15% total body surface area) and 147 traumatically-injured (injury severity score =8) patients across the ultra-early (=1 hour) and acute (4-72 hours) post-injury settings. Proinflammatory cytokine production by lipopolysaccharide (LPS) challenged whole blood leukocytes was studied, and plasma concentrations of total heme, and its scavengers haptoglobin, hemopexin and albumin measured, alongside the expression of heme-oxygenase-1 (HO-1) in peripheral blood mononuclear cells (PBMCs). LPS-induced tumour necrosis factor-alpha (TNFα) production by THP-1 cells and monocytes following in vitro heme treatment was also examined. Results: Burns and traumatic injury resulted in significantly elevated plasma concentrations of heme, which coincided with reduced levels of hemopexin and albumin, and correlated positively with circulating levels of pro and antiinflammatory cytokines. PBMCs isolated from trauma patients 4-12 and 48-72 hours post-injury exhibited increased HO-1 gene expression. Non-survivors of burn injury and patients who developed sepsis, presented on day 1 with significantly elevated heme levels, with a difference of 6.5 µM in heme concentrations corresponding to a relative 52% increase in the odds of postburn mortality. On day 1 post-burn, heme levels were negatively associated with ex vivo LPS-induced TNF-α and interleukin-6 production by whole blood leukocytes. THP-1 cells and monocytes pre-treated with heme exhibited significantly reduced TNF-α production following LPS stimulation. This impairment was associated with decreased gene transcription, reduced activation of extracellular signal-regulated kinase 1/2 and an impaired glycolytic response. Conclusions: Major injury results in elevated plasma concentrations of total heme that may contribute to the development of endotoxin tolerance and increase the risk of poor clinical outcomes. Restoration of the heme scavenging system could be a therapeutic approach by which to improve immune function post-injury. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges.
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Pathania, Anup Singh
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TUMORS in children , *IMMUNOTHERAPY , *ANTINEOPLASTIC agents , *IMMUNE system , *SYMPTOMS , *METASTASIS , *IMMUNE checkpoint inhibitors , *CELL lines , *IMMUNOSUPPRESSION - Abstract
Simple Summary: The immune microenvironment surrounding a growing tumor is complex and diverse. Understanding this complexity is crucial for predicting prognosis and response to cancer therapy. Various immune cells, signaling molecules, and extracellular matrix components within this microenvironment interact intricately, influencing tumor progression and treatment effectiveness. A deeper understanding of these interactions can lead to better prognostic markers and more effective, personalized therapeutic strategies. Compared to adults, the pediatric tumor immune microenvironment is less studied. Research on different pediatric tumors has shown that regulatory signaling networks between tumors and surrounding immune cells are critical in shifting the balance between pro- and anti-tumor immune responses. Therefore, gaining insights into the tumor immune composition is key to improving the efficacy of various pediatric cancer therapies, particularly immunotherapies that enhance host anti-tumor immunity. The tumor immune microenvironment is pivotal in cancer initiation, advancement, and regulation. Its molecular and cellular composition is critical throughout the disease, as it can influence the balance between suppressive and cytotoxic immune responses within the tumor's vicinity. Studies on the tumor immune microenvironment have enriched our understanding of the intricate interplay between tumors and their immunological surroundings in various human cancers. These studies illuminate the role of significant components of the immune microenvironment, which have not been extensively explored in pediatric tumors before and may influence the responsiveness or resistance to therapeutic agents. Our deepening understanding of the pediatric tumor immune microenvironment is helping to overcome challenges related to the effectiveness of existing therapeutic strategies, including immunotherapies. Although in the early stages, targeted therapies that modulate the tumor immune microenvironment of pediatric solid tumors hold promise for improved outcomes. Focusing on various aspects of tumor immune biology in pediatric patients presents a therapeutic opportunity that could improve treatment outcomes. This review offers a comprehensive examination of recent literature concerning profiling the immune microenvironment in various pediatric tumors. It seeks to condense research findings on characterizing the immune microenvironment in pediatric tumors and its impact on tumor development, metastasis, and response to therapeutic modalities. It covers the immune microenvironment's role in tumor development, interactions with tumor cells, and its impact on the tumor's response to immunotherapy. The review also discusses challenges targeting the immune microenvironment for pediatric cancer therapies. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Modulation of cyclophosphamide-induced immunosuppression and intestinal flora in broiler by deep eutectic solvent extracted polysaccharides of Acanthopanax senticosus.
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Jianqing Su, Jiaojiao Xue, Xueyan Wang, Rui Zhang, Xueping Zhang, Yaosen Yang, and Xiuling Chu
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ACANTHOPANAX ,BOTANY ,ENZYME-linked immunosorbent assay ,INTESTINES ,IMMUNOSUPPRESSION - Abstract
Introduction: The aim of this experiment was to investigate the modulation effect of Acanthopanax senticosus polysaccharide (ASPS-PD) extracted with deep eutectic solvent on cyclophosphamide-induced immunosuppression in broilers and its modulation of the gut microbiota of broilers. Methods: The 108 one-day-old broilers were divided into six groups, including the control group, the Cyclophosphamide (CY) model group, the ASPS-PD control group, the ASPA-PD high and low dose groups and the Astragalus polysaccharide group. Body weight, feed intake, feed conversion ratio, and immune organ index of broilers at 7, 14, and 21 days were determined; IL-2, IFN-γ, and lgG1 levels were determined by enzyme-linked immunosorbent assay (ELISA); Broiler caeca feces were analyzed by amplification and 16S rRNA sequencing. Results: The results showed that ASPS-PD can restore growth performance, increase immune organ index and improve serumcytokine levels of IL-2 and IFN-γ and immunoglobulin lgG1 levels in CY-treated broilers. The analysis of cecum flora showed that ASPS-PD can promote the proliferation of beneficial bacteria and reduce the number of harmful bacteria, regulating intestinal flora. Discussion: Therefore, ASPA-PD may be a potential novel immunomodulator to ameliorate CY-induced immunosuppression and intestinal flora dysregulation in broiler. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Host aphid immunosuppression by Aphidius ervi venom.
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Russo, Elia, Becchimanzi, Andrea, Magoga, Giulia, Montagna, Matteo, Di Lelio, Ilaria, and Pennacchio, Francesco
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PEA aphid , *VENOM , *RNA interference , *APHIDS , *SMALL interfering RNA , *PARASITIC wasps - Abstract
The host immunosuppression by parasitic wasps is an important component of the host regulation strategy. The venom injected at the oviposition is one of the key‐factors involved in this host alteration and, in some parasitoids, its immunosuppressive role is complemented by wasp's symbionts. Most studies in this research area are related to hosts belonging to Lepidoptera and Diptera, for which a strong immune response is observed, whereas little is known for hemimetabolous host species, characterized by apparently much weaker defense barriers. To fill this research gap, here we focus on the host–parasitoid system Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae) – Aphidius ervi Haliday (Hymenoptera: Braconidae). We functionally characterized a serine protease homolog (AeSPH) protein in vivo, identified in the venom of the aphid endoparasitoid A. ervi, generating AeSPH‐depleted female wasps by RNA interference and evaluating their capacity to successfully parasitize the host. Parasitism success rate was negatively affected by AeSPH knockdown and associated with an increased phenoloxidase (PO) cascade activation in aphids, scored by measuring PO enzymatic activity and the expression of phenoloxidase activating factor 2, a proPO‐activating gene upregulated in response to A. ervi parasitism. Our results indicate that AeSPH contributes to parasitism success by inhibiting the melanization response of the host, which is therefore an important component of the defense barriers involved in the parasitoid egg suppression. The ongoing studies on other virulence factors in A. ervi venom will allow to further characterize the immunosuppression strategy and its possible broader role in the host regulation through its action on aphid symbiont development. [ABSTRACT FROM AUTHOR]
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- 2024
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13. GDF15: Immunomodulatory Role in Hepatocellular Carcinoma Pathogenesis and Therapeutic Implications.
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Du, Yi-Ning and Zhao, Jin-Wei
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GROWTH differentiation factors ,HEPATIC fibrosis ,FATTY liver ,PROGNOSIS ,LIVER cells ,HEPATOCELLULAR carcinoma - Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally and the sixth most common cancer worldwide. Evidence shows that growth differentiation factor 15 (GDF15) contributes to hepatocarcinogenesis through various mechanisms. This paper reviews the latest insights into the role of GDF15 in the development of HCC, its role in the immune microenvironment of HCC, and its molecular mechanisms in metabolic dysfunction associated steatohepatitis (MASH) and metabolic associated fatty liver disease (MAFLD)-related HCC. Additionally, as a serum biomarker for HCC, diagnostic and prognostic value of GDF15 for HCC is summarized. The article elaborates on the immunological effects of GDF15, elucidating its effects on hepatic stellate cells (HSCs), liver fibrosis, as well as its role in HCC metastasis and tumor angiogenesis, and its interactions with anticancer drugs. Based on the impact of GDF15 on the immune response in HCC, future research should identify its signaling pathways, affected immune cells, and tumor microenvironment interactions. Clinical studies correlating GDF15 levels with patient outcomes can aid personalized treatment. Additionally, exploring GDF15-targeted therapies with immunotherapies could improve anti-tumor responses and patient outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Beet Supplementation, Exercise, Inflammation
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Standard Process
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- 2023
15. Early Severe Illness TrAnslational BioLogy InformaticS in Humans (ESTABLISH)
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London Health Sciences Centre, Western University, Canada, Western University, and Aleks Leligdowicz, Clinician Scientist
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- 2023
16. Comparison of efficacy and safety of tofacitinib and azathioprine in patients with alopecia areata and variants: a double-blind, randomized controlled trial.
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Paracha, Majid, Wasim, Muhammad, Noor, Sahibzada M., Khan, Abdul Q., Sagheer, Farah, and Ahmad, Iftikhar
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Background: Alopecia areata (AA) is an autoimmune pathology manifested by loss of hair. Objective: To evaluate and compare the efficacy and safety of tofacitinib and azathioprine in patients with AA and variants. Methods: In this double-blind randomized controlled trail (RCT) carried out at the Department of Dermatology, Medical Teaching Institute-Lady Reading Hospital (MTI-LRH), Peshawar, Pakistan, patients aged ≥ 12 years diagnosed with AA, alopecia totalis (AT) or alopecia universalis (AU) with minimum 50% scalp hair loss for a period ≥ 06 years were included. Patients were randomly assigned to receive oral tofacitinib 5 mg twice daily (Group I) or oral azathioprine 2 mg/kg body weight once daily (Group II). The primary endpoint was Severity of Alopecia Tool (SALT) score, evaluated at baseline and 06 months follow-up. Safety was consistently assessed during the study. Results: A total of 104 patients underwent random allocation into either the tofacitinib group (n = 52) or the azathioprine group (n = 52). The mean (SD) age of patients was 20.23 (7.14) years and 22.26 (8.07) years, while the mean (SD) disease duration was 6.59 (4.01) years and 7.98 (4.40) years in in Group I and II, respectively. Overall, 40 (38.5%) patients were adolescents while 70 (67.3%) were male. 52 (50%) had AA, 37 (35.5%) had AT and 15 (14.5%) had AU. Mean baseline SALT score in tofacitinib group was 91.02 ± 10.21 and azathioprine group was 91.02 ± 10.63, which at 06 months follow-up improved to 14.1 ± 24.6 and 63.9 ± 33.9, respectively (difference, 11.5 points; 95% confidence interval, 38.3–61.3, p < 0.0001). Overall, no major adverse effects and no difference among the minor adverse effects in the two groups (04 adverse events for tofacitinib group and 08 for azathioprine group: p = 0.23) was observed. Conclusions: Efficacy of tofacitinib was significantly higher than azathioprine, whilst both drugs were well-tolerated in patients with AA and variants. [ABSTRACT FROM AUTHOR]
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- 2024
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17. The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk
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Soheil Rahmati, Aysan Moeinafshar, and Nima Rezaei
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Extracellular vesicles ,Exosomes ,Colorectal cancer ,Metastasis ,Immune suppression ,Therapy resistance ,Medicine - Abstract
Abstract Extracellular vesicles (EVs) are lipid bilayer structures released by all cells and widely distributed in all biological fluids. EVs are implicated in diverse physiopathological processes by orchestrating cell–cell communication. Colorectal cancer (CRC) is one of the most common cancers worldwide, with metastasis being the leading cause of mortality in CRC patients. EVs contribute significantly to the advancement and spread of CRC by transferring their cargo, which includes lipids, proteins, RNAs, and DNAs, to neighboring or distant cells. Besides, they can serve as non-invasive diagnostic and prognostic biomarkers for early detection of CRC or be harnessed as effective carriers for delivering therapeutic agents. Autophagy is an essential cellular process that serves to remove damaged proteins and organelles by lysosomal degradation to maintain cellular homeostasis. Autophagy and EV release are coordinately activated in tumor cells and share common factors and regulatory mechanisms. Although the significance of autophagy and EVs in cancer is well established, the exact mechanism of their interplay in tumor development is obscure. This review focuses on examining the specific functions of EVs in various aspects of CRC, including progression, metastasis, immune regulation, and therapy resistance. Further, we overview emerging discoveries relevant to autophagy and EVs crosstalk in CRC.
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- 2024
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18. The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies
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Longsheng Wang, Jie Zhang, Wenxin Zhang, Mingming Zheng, Hongjie Guo, Xiaohui Pan, Wen Li, Bo Yang, and Ling Ding
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Adenosine ,Adenosine receptors ,Adenosine-generating enzymes ,Tumor microenvironment ,Immune suppression ,Immune escape ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Adenosine (Ado) is significantly elevated in the tumor microenvironment (TME) compared to normal tissues. It binds to adenosine receptors (AdoRs), suppressing tumor antigen presentation and immune cell activation, thereby inhibiting tumor adaptive immunity. Ado downregulates major histocompatibility complex II (MHC II) and co-stimulatory factors on dendritic cells (DCs) and macrophages, inhibiting antigen presentation. It suppresses anti-tumor cytokine secretion and T cell activation by disrupting T cell receptor (TCR) binding and signal transduction. Ado also inhibits chemokine secretion and KCa3.1 channel activity, impeding effector T cell trafficking and infiltration into the tumor site. Furthermore, Ado diminishes T cell cytotoxicity against tumor cells by promoting immune-suppressive cytokine secretion, upregulating immune checkpoint proteins, and enhancing immune-suppressive cell activity. Reducing Ado production in the TME can significantly enhance anti-tumor immune responses and improve the efficacy of other immunotherapies. Preclinical and clinical development of inhibitors targeting Ado generation or AdoRs is underway. Therefore, this article will summarize and analyze the inhibitory effects and molecular mechanisms of Ado on tumor adaptive immunity, as well as provide an overview of the latest advancements in targeting Ado pathways in anti-tumor immune responses.
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- 2024
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19. Revealing the role of SPP1+ macrophages in glioma prognosis and therapeutic targeting by investigating tumor-associated macrophage landscape in grade 2 and 3 gliomas
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Wenshu Tang, Cario W. S. Lo, Wei Ma, Annie T. W. Chu, Amy H. Y. Tong, and Brian H. Y. Chung
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Glioma ,Tumor-associated macrophages ,TAM-SPP1 ,EGFR ,Immune suppression ,Biotechnology ,TP248.13-248.65 ,Biology (General) ,QH301-705.5 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Glioma is a highly heterogeneous brain tumor categorized into World Health Organization (WHO) grades 1–4 based on its malignancy. The suppressive immune microenvironment of glioma contributes significantly to unfavourable patient outcomes. However, the cellular composition and their complex interplays within the glioma environment remain poorly understood, and reliable prognostic markers remain elusive. Therefore, in-depth exploration of the tumor microenvironment (TME) and identification of predictive markers are crucial for improving the clinical management of glioma patients. Results Our analysis of single-cell RNA-sequencing data from glioma samples unveiled the immunosuppressive role of tumor-associated macrophages (TAMs), mediated through intricate interactions with tumor cells and lymphocytes. We also discovered the heterogeneity within TAMs, among which a group of suppressive TAMs named TAM-SPP1 demonstrated a significant association with Epidermal Growth Factor Receptor (EGFR) amplification, impaired T cell response and unfavourable patient survival outcomes. Furthermore, by leveraging genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) dataset, two distinct molecular subtypes with a different constitution of TAMs, EGFR status and clinical outcomes were identified. Exploiting the molecular differences between these two subtypes, we developed a four-gene-based prognostic model. This model displayed strong associations with an elevated level of suppressive TAMs and could be used to predict anti-tumor immune response and prognosis in glioma patients. Conclusion Our findings illuminated the molecular and cellular mechanisms that shape the immunosuppressive microenvironment in gliomas, providing novel insights into potential therapeutic targets. Furthermore, the developed prognostic model holds promise for predicting immunotherapy response and assisting in more precise risk stratification for glioma patients. Graphical abstract
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- 2024
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20. Identification of BACH1-IT2-miR-4786-Siglec-15 immune suppressive axis in bladder cancer
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Xingzhi Li, Ziji Liang, Jiexin Pan, Meng Zhang, Jinli Liu, Rong Hu, and Caiyan Liao
- Subjects
Bladder cancer ,BACH1-IT2 ,Siglec-15 ,miR-4786 ,Immune suppression ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract The sialic acid binding Ig like lectin 15 (Siglec-15) was previously identified as tumor immune suppressor gene in some human cancers with elusive molecular mechanism to be elucidated. The continuous focus on both clinical and basic biology of bladder cancer leads us to characterize aberrant abundance of BACH1-IT2 associating with stabilization of Siglec-15, which eventually contributes to local immune suppressive microenvironment and therefore tumor advance. This effect was evidently mediated by miR-4786-5p. BACH1-IT2 functions in this scenario as microRNA sponge, and competitively conceals miR-4786 and up-regulates cancer cell surface Siglec-15. The BACH1-IT2-miR-4786-Siglec-15 axis significantly influences activation of immune cell co-culture. In summary, our data highlights the critical involvements of BACH1-IT2 and miR-4786 in immune evasion in bladder cancer, which hints the potential for both therapeutic and prognostic exploitation.
- Published
- 2024
- Full Text
- View/download PDF
21. The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk.
- Author
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Rahmati, Soheil, Moeinafshar, Aysan, and Rezaei, Nima
- Subjects
- *
EXTRACELLULAR vesicles , *IMMUNOSUPPRESSION , *COLORECTAL cancer , *AUTOPHAGY , *METASTASIS , *BRAIN metastasis , *CHOLESTERYL ester transfer protein - Abstract
Extracellular vesicles (EVs) are lipid bilayer structures released by all cells and widely distributed in all biological fluids. EVs are implicated in diverse physiopathological processes by orchestrating cell–cell communication. Colorectal cancer (CRC) is one of the most common cancers worldwide, with metastasis being the leading cause of mortality in CRC patients. EVs contribute significantly to the advancement and spread of CRC by transferring their cargo, which includes lipids, proteins, RNAs, and DNAs, to neighboring or distant cells. Besides, they can serve as non-invasive diagnostic and prognostic biomarkers for early detection of CRC or be harnessed as effective carriers for delivering therapeutic agents. Autophagy is an essential cellular process that serves to remove damaged proteins and organelles by lysosomal degradation to maintain cellular homeostasis. Autophagy and EV release are coordinately activated in tumor cells and share common factors and regulatory mechanisms. Although the significance of autophagy and EVs in cancer is well established, the exact mechanism of their interplay in tumor development is obscure. This review focuses on examining the specific functions of EVs in various aspects of CRC, including progression, metastasis, immune regulation, and therapy resistance. Further, we overview emerging discoveries relevant to autophagy and EVs crosstalk in CRC. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
22. Signaling crosstalk between tumor endothelial cells and immune cells in the microenvironment of solid tumors.
- Author
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Xu, Yuexin, Miller, Chris P., Tykodi, Scott S., Akilesh, Shreeram, and Warren, Edus H.
- Subjects
ENDOTHELIAL cells ,TUMOR-infiltrating immune cells ,TUMOR microenvironment ,VASCULAR endothelial growth factors ,GROWTH factors ,ENDOTHELIUM diseases - Abstract
Tumor-associated endothelial cells (TECs) are crucial mediators of immune surveillance and immune escape in the tumor microenvironment (TME). TECs driven by angiogenic growth factors form an abnormal vasculature which deploys molecular machinery to selectively promote the function and recruitment of immunosuppressive cells while simultaneously blocking the entry and function of anti-tumor immune cells. TECs also utilize a similar set of signaling regulators to promote the metastasis of tumor cells. Meanwhile, the tumor-infiltrating immune cells further induce the TEC anergy by secreting pro-angiogenic factors and prevents further immune cell penetration into the TME. Understanding the complex interactions between TECs and immune cells will be needed to successfully treat cancer patients with combined therapy to achieve vasculature normalization while augmenting antitumor immunity. In this review, we will discuss what is known about the signaling crosstalk between TECs and tumor-infiltrating immune cells to reveal insights and strategies for therapeutic targeting. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
23. The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies.
- Author
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Wang, Longsheng, Zhang, Jie, Zhang, Wenxin, Zheng, Mingming, Guo, Hongjie, Pan, Xiaohui, Li, Wen, Yang, Bo, and Ding, Ling
- Subjects
ADENOSINES ,IMMUNE checkpoint proteins ,T cell receptors ,ANTIGEN presentation ,IMMUNITY ,MAJOR histocompatibility complex - Abstract
Adenosine (Ado) is significantly elevated in the tumor microenvironment (TME) compared to normal tissues. It binds to adenosine receptors (AdoRs), suppressing tumor antigen presentation and immune cell activation, thereby inhibiting tumor adaptive immunity. Ado downregulates major histocompatibility complex II (MHC II) and co-stimulatory factors on dendritic cells (DCs) and macrophages, inhibiting antigen presentation. It suppresses anti-tumor cytokine secretion and T cell activation by disrupting T cell receptor (TCR) binding and signal transduction. Ado also inhibits chemokine secretion and KCa3.1 channel activity, impeding effector T cell trafficking and infiltration into the tumor site. Furthermore, Ado diminishes T cell cytotoxicity against tumor cells by promoting immune-suppressive cytokine secretion, upregulating immune checkpoint proteins, and enhancing immune-suppressive cell activity. Reducing Ado production in the TME can significantly enhance anti-tumor immune responses and improve the efficacy of other immunotherapies. Preclinical and clinical development of inhibitors targeting Ado generation or AdoRs is underway. Therefore, this article will summarize and analyze the inhibitory effects and molecular mechanisms of Ado on tumor adaptive immunity, as well as provide an overview of the latest advancements in targeting Ado pathways in anti-tumor immune responses. Adenosine suppresses tumor immune cells within the tumor microenvironment by inhibiting antigen presentation, T-cell activation and infiltration, and T-cell-mediated killing of tumor cells, thereby impairing tumor adaptive immunity. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
24. Effects of Chemotherapy on the Immune System: Implications for Cancer Treatment and Patient Outcomes.
- Author
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Sharma, Anirudh, Jasrotia, Shivam, and Kumar, Ajay
- Subjects
IMMUNE system ,CANCER prognosis ,IMMUNOSUPPRESSION ,ADJUVANT chemotherapy ,CANCER chemotherapy - Abstract
Chemotherapy is a cornerstone of cancer treatment, but it can also induce immune suppression, which can have significant implications for patient outcomes. This review paper aims to give a general overview of how chemotherapy affects the immune system and how it affects cancer treatment. Chemotherapy can directly affect immune cells, leading to cytotoxic effects, cell differentiation and function alterations, and cell communication and signaling pathways disruptions. Such immune suppression can weaken the anti-tumor immune response and increase the risk of immune-related toxicities. Understanding the mechanisms of chemotherapy-induced immune suppression is crucial for optimizing treatment strategies. Strategies to mitigate immune suppression include immunomodulatory agents as adjuvants to chemotherapy, combination therapies to enhance immune function, and supportive care measures of the immune system. Additionally, identifying potential biomarkers to predict immune suppression and guide treatment decisions holds promise for personalized cancer medicine. Future directions in this field involve further elucidating underlying mechanisms, exploring novel combination therapies, and developing targeted interventions to minimize immune suppression. By understanding and addressing chemotherapy-induced immune suppression, we can optimize cancer treatment strategies, enhance the anti-tumor immune response, and improve patient outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
25. Alteration of functionality and differentiation directed by changing gene expression patterns in myeloid-derived suppressor cells (MDSCs) in tumor microenvironment and bone marrow through early to terminal phase of tumor progression.
- Author
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Mahanti, Krishna, Saha, Jayasree, Sarkar, Debanjan, Pramanik, Anik, Chattopadhyay, Nabanita Roy, and Bhattacharyya, Sankar
- Subjects
MYELOID-derived suppressor cells ,BONE marrow cancer ,GENE expression ,MYELOID cells ,CANCER invasiveness ,CANCER cell differentiation - Abstract
Myeloid-derived suppressor cells are heterogenous immature myeloid lineage cells that can differentiate into neutrophils, monocytes, and dendritic cells as well. These cells have been characterized to have potent immunosuppressive capacity in neoplasia and a neoplastic chronic inflammatory microenvironment. Increased accumulation of myeloid-derived suppressor cells was reported with poor clinical outcomes in patients. They support neoplastic progression by abrogating antitumor immunity through inhibition of lymphocyte functions and directly by facilitating tumor development. Yet the shifting genetic signatures of this myeloid lineage cell toward immunosuppressive functionality in progressive tumor development remain elusive. We have attempted to identify the gene expression profile using lineage-specific markers of these unique myeloid lineage cells in a tumor microenvironment and bone marrow using a liquid transplantable mice tumor model to trace the changing influence of the tumor microenvironment on myeloid-derived suppressor cells. We analyzed the phenotype, functional shift, suppressive activity, differentiation status, and microarray-based gene expression profile of CD11b
+ Gr1+ lineage-specific cells isolated from the tumor microenvironment and bone marrow of 4 stages of tumor-bearing mice and compared them with control counterparts. Our analysis of differentially expressed genes of myeloid-derived suppressor cells isolated from bone marrow and the tumor microenvironment reveals unique gene expression patterns in the bone marrow and tumor microenvironment–derived myeloid-derived suppressor cells. It also suggests T-cell suppressive activity of myeloid-derived suppressor cells progressively increases toward the mid-to-late phase of the tumor and a significant differentiation bias of tumor site myeloid-derived suppressor cells toward macrophages, even in the presence of differentiating agents, indicating potential molecular characteristics of myeloid-derived suppressor cells in different stages of the tumor that can emerge as an intervention target. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
26. Revealing the role of SPP1+ macrophages in glioma prognosis and therapeutic targeting by investigating tumor-associated macrophage landscape in grade 2 and 3 gliomas.
- Author
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Tang, Wenshu, Lo, Cario W. S., Ma, Wei, Chu, Annie T. W., Tong, Amy H. Y., and Chung, Brian H. Y.
- Subjects
- *
EPIDERMAL growth factor receptors , *GLIOMAS , *T cells , *GENE amplification , *DRUG target , *BRAIN tumors , *IMMUNOSUPPRESSION - Abstract
Background: Glioma is a highly heterogeneous brain tumor categorized into World Health Organization (WHO) grades 1–4 based on its malignancy. The suppressive immune microenvironment of glioma contributes significantly to unfavourable patient outcomes. However, the cellular composition and their complex interplays within the glioma environment remain poorly understood, and reliable prognostic markers remain elusive. Therefore, in-depth exploration of the tumor microenvironment (TME) and identification of predictive markers are crucial for improving the clinical management of glioma patients. Results: Our analysis of single-cell RNA-sequencing data from glioma samples unveiled the immunosuppressive role of tumor-associated macrophages (TAMs), mediated through intricate interactions with tumor cells and lymphocytes. We also discovered the heterogeneity within TAMs, among which a group of suppressive TAMs named TAM-SPP1 demonstrated a significant association with Epidermal Growth Factor Receptor (EGFR) amplification, impaired T cell response and unfavourable patient survival outcomes. Furthermore, by leveraging genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) dataset, two distinct molecular subtypes with a different constitution of TAMs, EGFR status and clinical outcomes were identified. Exploiting the molecular differences between these two subtypes, we developed a four-gene-based prognostic model. This model displayed strong associations with an elevated level of suppressive TAMs and could be used to predict anti-tumor immune response and prognosis in glioma patients. Conclusion: Our findings illuminated the molecular and cellular mechanisms that shape the immunosuppressive microenvironment in gliomas, providing novel insights into potential therapeutic targets. Furthermore, the developed prognostic model holds promise for predicting immunotherapy response and assisting in more precise risk stratification for glioma patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
27. Identification of BACH1-IT2-miR-4786-Siglec-15 immune suppressive axis in bladder cancer.
- Author
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Li, Xingzhi, Liang, Ziji, Pan, Jiexin, Zhang, Meng, Liu, Jinli, Hu, Rong, and Liao, Caiyan
- Subjects
- *
BLADDER cancer , *TUMOR suppressor genes , *SIALIC acids - Abstract
The sialic acid binding Ig like lectin 15 (Siglec-15) was previously identified as tumor immune suppressor gene in some human cancers with elusive molecular mechanism to be elucidated. The continuous focus on both clinical and basic biology of bladder cancer leads us to characterize aberrant abundance of BACH1-IT2 associating with stabilization of Siglec-15, which eventually contributes to local immune suppressive microenvironment and therefore tumor advance. This effect was evidently mediated by miR-4786-5p. BACH1-IT2 functions in this scenario as microRNA sponge, and competitively conceals miR-4786 and up-regulates cancer cell surface Siglec-15. The BACH1-IT2-miR-4786-Siglec-15 axis significantly influences activation of immune cell co-culture. In summary, our data highlights the critical involvements of BACH1-IT2 and miR-4786 in immune evasion in bladder cancer, which hints the potential for both therapeutic and prognostic exploitation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
28. Immune evasion by Cryptococcus gattii in vaccinated mice coinfected with C. neoformans.
- Author
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Hester, Maureen M., Carlson, Diana, Lodge, Jennifer K., Levitz, Stuart M., and Specht, Charles A.
- Subjects
VACCINE effectiveness ,VACCINATION ,CRYPTOCOCCUS ,FUNGAL virulence ,CRYPTOCOCCUS neoformans ,MICE - Abstract
Cryptococcus neoformans and C. gattii, the etiologic agents of cryptococcosis, cause over 100,000 deaths worldwide every year, yet no cryptococcal vaccine has progressed to clinical trials. In preclinical studies, mice vaccinated with an attenuated strain of C. neoformans deleted of three cryptococcal chitin deacetylases (Cn-cda1Δ2Δ3Δ) were protected against a lethal challenge with C. neoformans strain KN99. While Cn-cda1Δ2Δ3Δ extended the survival of mice infected with C. gattii strain R265 compared to unvaccinated groups, we were unable to demonstrate fungal clearance as robust as that seen following KN99 challenge. In stark contrast to vaccinated mice challenged with KN99, we also found that R265-challenged mice failed to induce the production of protectionassociated cytokines and chemokines in the lungs. To investigate deficiencies in the vaccine response to R265 infection, we developed a KN99-R265 coinfection model. In unvaccinated mice, the strains behaved in a manner which mirrored single infections, wherein only KN99 disseminated to the brain and spleen. We expanded the coinfection model to Cn-cda1Δ2Δ3Δ-vaccinated mice. Fungal burden, cytokine production, and immune cell infiltration in the lungs of vaccinated, coinfected mice were indicative of immune evasion by C. gattii R265 as the presence of R265 neither compromised the immunophenotype established in response to KN99 nor inhibited clearance of KN99. Collectively, these data indicate that R265 does not dampen a protective vaccine response, but rather suggest that R265 remains largely undetected by the immune system. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
29. Risk of SARS‐CoV‐2 following joint and epidural corticosteroid injections: A retrospective study.
- Author
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Raju, Robin, Holder, Eric K., Dundas, Mark, Liang, Jingchen, and Donham, Rebecca
- Subjects
- *
ADRENOCORTICAL hormones , *IMMUNIZATION , *POLYMERASE chain reaction , *EPIDURAL injections , *RETROSPECTIVE studies , *TERTIARY care , *DESCRIPTIVE statistics , *MULTIVARIATE analysis , *AGE distribution , *JOINTS (Anatomy) , *PHYSIATRISTS , *MEDICAL records , *ACQUISITION of data , *COVID-19 , *IMMUNOSUPPRESSION , *REGRESSION analysis , *COMORBIDITY - Abstract
Objective: The immunosuppressive effects of corticosteroid (CS) injections have come under more scrutiny during the coronavirus disease 2019 (COVID‐19) pandemic. The aim of the study was to explore any relationship between joint/epidural CS injection and SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus 2) polymerase chain reaction (PCR) positivity. Methods: A retrospective chart review was conducted on patients 18 years or over who received at least one joint or epidural CS injection by physiatrists in a tertiary care center between January 1, 2020, and December 31, 2021. This cohort of patients was then compared to a control group who did not receive any CS injection during this time period. Results: A total of 766 patients were identified in the CS injection group and 1546 patients in the control group. Overall, 12.27% of patients turned SARS‐CoV‐2 PCR positive in the CS injection group, which was similar to 11.90% in the control group (p = 0.797). But 3‐month SARS‐CoV‐2 PCR positivity rate showed a statistically significant higher rate among the CS injection group (3.30% in the CS injection group vs. 2.10% in the control group; p = 0.027). In multivariate regression analysis, after adjusting both groups for Charlson Comorbidity Index (CCI), there was statistically significant higher SARS‐CoV‐2 PCR positivity rate in the CS injection group (p = 0.024). However, after adjusting both groups for age and total number of comorbidities, there was no difference between the groups in regard to SARS‐CoV‐2 PCR positivity rate (p = 0.081). In the subgroup analysis of only COVID‐19 vaccinated patients, there was an increased 3‐month SARS‐CoV‐2 PCR positivity rate among patients with severe comorbidities in the CS injection group (p = 0.036). Conclusion: The study was not conclusive on the effect of joint or epidural CS injection on SARS‐CoV‐2 PCR positivity rate, although adjusted analysis suggests higher 3‐month SARS‐CoV‐2 PCR positivity rate after CS injection in patients with severe comorbidities with significant disease burden when compared to controls. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
30. Fungal infection of insects: molecular insights and prospects.
- Author
-
Hong, Song, Shang, Junmei, Sun, Yaneli, Tang, Guirong, and Wang, Chengshu
- Subjects
- *
MYCOSES , *INSECT-fungus relationships , *PHYTOPATHOGENIC fungi , *ENTOMOPATHOGENIC fungi , *INSECT populations , *PHYTOPATHOGENIC microorganisms - Abstract
Entomopathogenic fungi (EPF), which have convergently evolved from different fungal phyla, play a pivotal role in regulating insect populations by infecting hosts via cuticle penetration instead of per os ingestion. Ascomycete EPF are evolutionarily closer to plant pathogenic fungi rather than mammalian pathogens, and the representative species have been developed and used in agriculture as ecofriendly mycoinsecticides. The stepwise infection of EPF can be divided into two essential processes: cuticle penetration and hemocoel colonization. Diverse genes, pathways, and small molecules have been characterized with specific contributions to fungal infection steps. EPF also have to outcompete insect cuticular microbiotas before they can breach insect cuticles, which expands the bilateral fungus–insect interactions to a multipartite level. Further investigations of EPF virulence effectors, chemical biology, and epigenetic controls will deepen our understanding of EPF pathobiology and pathoecology. Entomopathogenic fungi (EPF) distribute in different fungal phyla with variable host ranges and play essential role in regulating insect populations by infecting hosts via cuticle penetration. The representative ascomycete EPF of Metarhizium and Beauveria species have been widely used in mechanistic investigations of fungus–insect interactions and as ecofriendly mycoinsecticides. Here, we review the function of diverse genes, pathways, and secondary metabolites associated with EPF stepwise infections. In particular, emerging evidence has shown that EPF have to outcompete insect ectomicrobiotas prior to penetrating cuticles, and subvert or evade host antifungal immunity by using effector-like proteins and chemicals like plant pathogens. Future prospects are discussed for a better understanding of fungal pathobiology, which will provide novel insights into microbe–animal interactions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
31. Mitochondrial‐targeted curcumin inhibits T‐cell activation via Nrf2 and inhibits graft‐versus‐host‐disease in a mouse model.
- Author
-
Patwardhan, Raghavendra S., Gohil, Dievya, Singh, Babita, Kumar, Binita K., Purohit, Vaitashi, Thoh, Maikho, Checker, Rahul, Gardi, Nilesh, Gota, Vikram, Kutala, Vijay Kumar, Patwardhan, Sejal, Sharma, Deepak, and Sandur, Santosh K.
- Abstract
Anti‐inflammatory and immune suppressive agents are required to moderate hyper‐activation of lymphocytes under disease conditions or organ transplantation. However, selective disruption of mitochondrial redox has not been evaluated as a therapeutic strategy for suppression of T‐cell‐mediated pathologies. Using mitochondrial targeted curcumin (MitoC), we studied the effect of mitochondrial redox modulation on T‐cell responses by flow cytometry, transmission electron microscopy, transcriptomics, and proteomics, and the role of Nrf2 was studied using Nrf2−/− mice. MitoC decreased mitochondrial TrxR activity, enhanced mitochondrial ROS (mROS) production, depleted mitochondrial glutathione, and suppressed activation‐induced increase in mitochondrial biomass. This led to suppression of T‐cell responses and metabolic reprogramming towards Treg differentiation. MitoC induced nuclear translocation and DNA binding of Nrf2, leading to upregulation of Nrf2‐dependent genes and proteins. MitoC‐mediated changes in mitochondrial redox and modulation of T‐cell responses are abolished in Nrf2−/− mice. Restoration of mitochondrial thiols abrogated inhibition of T‐cell responses. MitoC suppressed alloantigen‐induced lymphoblast formation, inflammatory cytokines, morbidity, and mortality in acute graft‐versus‐host disease mice. Disruption of mitochondrial thiols but not mROS increase inculcates an Nrf2‐dependent immune‐suppressive disposition in T cells for the propitious treatment of graft‐versus‐host disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
32. Assessing the Burden and Cost of COVID-19 Across Variants in Commercially Insured Immunocompromised Populations in the United States: Updated Results and Trends from the Ongoing EPOCH-US Study.
- Author
-
Ketkar, Amita, Willey, Vincent, Glasser, Lisa, Dobie, Casey, Wenziger, Cachet, Teng, Chia-Chen, Dube, Christine, Hirpara, Sunny, Cunningham, Dennis, and Verduzco-Gutierrez, Monica
- Abstract
Introduction/Methods: EPOCH-US is an ongoing, retrospective, observational cohort study among individuals identified in the Healthcare Integrated Research Database (HIRD
® ) with ≥ 12 months of continuous health plan enrollment. Data were collected for the HIRD population (containing immunocompetent and immunocompromised [IC] individuals), individual IC cohorts (non-mutually exclusive cohorts based on immunocompromising condition and/or immunosuppressive [IS] treatment), and the composite IC population (all unique IC individuals). This study updates previous results with addition of the general population cohort and data specifically for the year of 2022 (i.e., Omicron wave period). To provide healthcare decision-makers the most recent trends, this study reports incidence rates (IR) and severity of first SARS-CoV-2 infection; and relative risk, healthcare utilization, and costs related to first COVID-19 hospitalizations in the full year of 2022 and overall between April 2020 and December 2022. Results: These updated results showed a 2.9% prevalence of immune compromise in the population. From April 2020 through December 2022, the overall IR of COVID-19 was 115.7 per 1000 patient-years in the composite IC cohort and 77.8 per 1000 patient-years in the HIRD cohort. The composite IC cohort had a 15.4% hospitalization rate with an average cost of $42,719 for first COVID-19 hospitalization. Comparatively, the HIRD cohort had a 3.7% hospitalization rate with an average cost of $28,848 for first COVID-19 hospitalization. Compared to the general population, IC individuals had 4.3 to 23 times greater risk of hospitalization with first diagnosis of COVID-19. Between January and December 2022, hospitalizations associated with first COVID-19 diagnosis cost over $1 billion, with IC individuals (~ 3% of the population) generating $310 million (31%) of these costs. Conclusion: While only 2.9% of the population, IC individuals had a higher risk of COVID-19 hospitalization and incurred higher healthcare costs across variants. They also disproportionately accounted for over 30% of total costs for first COVID-19 hospitalization in 2022, amounting to ~ $310 million. These data highlight the need for additional preventive measures to decrease the risk of developing severe COVID-19 outcomes in vulnerable IC populations. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
33. Effects of puerarin on growth, liver immunity and antioxidant capacity of yellowfin seabream (Acanthopagrus latus) under oxidized fish oil stress
- Author
-
Lumin Kong, Jianrong Ma, Sishun Zhou, Zhangfan Huang, Xiujuan Wang, Fuqiang Quan, Xi Zhao, Zhenyu Yi, Hao Lin, Longhui Liu, Wanting Luo, Yunting Zhao, and Zhongbao Li
- Subjects
Liver morphology ,Oxidative damage ,Immune suppression ,Aquaculture. Fisheries. Angling ,SH1-691 - Abstract
Puerarin, an isoflavone, exhibits protective effects against liver damage. This study investigated the effects of puerarin on the growth, liver immunity, and antioxidant capacity of yellowfin seabream fed with oxidized fish oil. A total of 135 yellowfin seabream (13.00±0.05 g) were randomly divided into nine tanks (15 fish per tank), and fed with three types of diets for 56 days: a normal control fed with 6 % fresh fish oil (NC), an experimental control fed with 6 % oxidized fish oil (OFO), and a treatment fed with 6 % oxidized fish oil and supplemented with 400 mg/kg puerarin (OFP). Results showed, oxidized fish oil decreased the growth of fish, caused liver damage, and suppressed the fish's immunity. Compared to the NC group, the weight gain (WG) and specific growth rate (SGR) of the fish in the OFO group were significantly reduced; the activities of superoxide dismutase (SOD) and catalase (CAT) in serum were significantly decreased; liver morphology showed loose cytoplasm with a large amount of fatty degeneration; the lysozyme (LZM) activity in serum and liver was significantly reduced. On the other hand, compared to the NC and OFO groups, the WG and SGR of fish in the OFP group were significantly improved. Additionally, compared to the OFO group, the serum SOD and liver CAT activities in the fish of the OFP group were significantly increased, and the MDA content in serum and liver was significantly reduced. The extensive fatty degeneration in the liver was alleviated. The LZM activity in the serum and liver of fish in the OFP group was significantly higher than that in the OFO group, returning to the levels of the NC group. Meanwhile, puerarin significantly enhanced the expression of Nrf2. In conclusion, puerarin alleviated the adverse reactions induced by oxidized fish oil and promoted the growth of yellowfin seabream.
- Published
- 2024
- Full Text
- View/download PDF
34. Tumor-produced immune regulatory factors as a therapeutic target in cancer treatment
- Author
-
Vladimir Rogovskii
- Subjects
cancer ,inflammation ,cytokines ,immune-regulatory factors ,immune suppression ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2024
- Full Text
- View/download PDF
35. Inflammation is a critical factor for successful regeneration of the adult zebrafish retina in response to diffuse light lesion
- Author
-
Oliver Bludau, Anke Weber, Viktoria Bosak, Veronika Kuscha, Kristin Dietrich, Stefan Hans, and Michael Brand
- Subjects
immune suppression ,M-CSF ,microglia ,Müller glia ,NF-κB pathway ,regeneration ,Biology (General) ,QH301-705.5 - Abstract
Inflammation can lead to persistent and irreversible loss of retinal neurons and photoreceptors in mammalian vertebrates. In contrast, in the adult zebrafish brain, acute neural inflammation is both necessary and sufficient to stimulate regeneration of neurons. Here, we report on the critical, positive role of the immune system to support retina regeneration in adult zebrafish. After sterile ablation of photoreceptors by phototoxicity, we find rapid response of immune cells, especially monocytes/microglia and neutrophils, which returns to homeostatic levels within 14 days post lesion. Pharmacological or genetic impairment of the immune system results in a reduced Müller glia stem cell response, seen as decreased reactive proliferation, and a strikingly reduced number of regenerated cells from them, including photoreceptors. Conversely, injection of the immune stimulators flagellin, zymosan, or M-CSF into the vitreous of the eye, leads to a robust proliferation response and the upregulation of regeneration-associated marker genes in Müller glia. Our results suggest that neuroinflammation is a necessary and sufficient driver for retinal regeneration in the adult zebrafish retina.
- Published
- 2024
- Full Text
- View/download PDF
36. Severe thermal and major traumatic injury results in elevated plasma concentrations of total heme that are associated with poor clinical outcomes and systemic immune suppression
- Author
-
Sebastian Tullie, Thomas Nicholson, Jonathan R. B. Bishop, Kirsty C. McGee, Ali Asiri, Jack Sullivan, Yung-Yi Chen, Amanda V. Sardeli, Antonio Belli, Paul Harrison, Naiem S. Moiemen, Janet M. Lord, and Jon Hazeldine
- Subjects
burns ,critical care ,heme ,immune suppression ,trauma ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundTraumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from injured muscle and lysed red blood cells, heme is a damage associated molecular pattern with potent immune modulatory properties. Here, we measured plasma concentrations of total heme in over 200 traumatic and thermally-injured patients in order to examine its relationship with clinical outcomes and post-injury immune suppression.MethodsBlood samples were collected from 98 burns (≥15% total body surface area) and 147 traumatically-injured (injury severity score ≥8) patients across the ultra-early (≤1 hour) and acute (4–72 hours) post-injury settings. Pro-inflammatory cytokine production by lipopolysaccharide (LPS) challenged whole blood leukocytes was studied, and plasma concentrations of total heme, and its scavengers haptoglobin, hemopexin and albumin measured, alongside the expression of heme-oxygenase-1 (HO-1) in peripheral blood mononuclear cells (PBMCs). LPS-induced tumour necrosis factor-alpha (TNF-α) production by THP-1 cells and monocytes following in vitro heme treatment was also examined.ResultsBurns and traumatic injury resulted in significantly elevated plasma concentrations of heme, which coincided with reduced levels of hemopexin and albumin, and correlated positively with circulating levels of pro and anti-inflammatory cytokines. PBMCs isolated from trauma patients 4–12 and 48–72 hours post-injury exhibited increased HO-1 gene expression. Non-survivors of burn injury and patients who developed sepsis, presented on day 1 with significantly elevated heme levels, with a difference of 6.5 µM in heme concentrations corresponding to a relative 52% increase in the odds of post-burn mortality. On day 1 post-burn, heme levels were negatively associated with ex vivo LPS-induced TNF-α and interleukin-6 production by whole blood leukocytes. THP-1 cells and monocytes pre-treated with heme exhibited significantly reduced TNF-α production following LPS stimulation. This impairment was associated with decreased gene transcription, reduced activation of extracellular signal-regulated kinase 1/2 and an impaired glycolytic response.ConclusionsMajor injury results in elevated plasma concentrations of total heme that may contribute to the development of endotoxin tolerance and increase the risk of poor clinical outcomes. Restoration of the heme scavenging system could be a therapeutic approach by which to improve immune function post-injury.
- Published
- 2024
- Full Text
- View/download PDF
37. Immune and Inflammatory Indices in Peripheral Blood Predict Prognosis of Glioma and Correlate With Grades and Subtypes
- Author
-
Yonggao Mou, Clinical Professor
- Published
- 2023
38. Supplementary Epidural Analgesia in Video-Assisted Thoracic Surgery (VATS) - The SEAVATS Study (SEAVATS)
- Author
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Jimmy Højberg Holm, MD
- Published
- 2023
39. Astaxanthin, Exercise Inflammation, Skin Health
- Author
-
LycoRed Ltd.
- Published
- 2023
40. Cytomegalovirus (CMV) Reactivation in Allogeneic HSCT Recipient (CReSCT)
- Author
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Peter MacCallum Cancer Centre, Australia, Western Sydney Local Health District, Walter and Eliza Hall Institute of Medical Research, Austin Hospital, Melbourne Australia, and Monica Slavin, Infectious Diseases Physician
- Published
- 2023
41. Targeting macrophage Syk enhances responses to immune checkpoint blockade and radiotherapy in high-risk neuroblastoma
- Author
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Rohila, Deepak, Park, In Hwan, Pham, Timothy V, Jones, Riley, Tapia, Elisabette, Liu, Kevin X, Tamayo, Pablo, Yu, Alice, Sharabi, Andrew B, and Joshi, Shweta
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Neuroblastoma ,Cancer ,Pediatric ,Neurosciences ,Immunotherapy ,Orphan Drug ,Rare Diseases ,Pediatric Cancer ,Animals ,Mice ,Immune Checkpoint Inhibitors ,N-Myc Proto-Oncogene Protein ,Macrophages ,Tumor Microenvironment ,macrophage ,neuroblastoma ,immune suppression ,Syk ,T cells ,Medical Microbiology ,Biochemistry and cell biology ,Genetics - Abstract
BackgroundNeuroblastoma (NB) is considered an immunologically cold tumor and is usually less responsive to immune checkpoint blockade (ICB). Tumor-associated macrophages (TAMs) are highly infiltrated in NB tumors and promote immune escape and resistance to ICB. Hence therapeutic strategies targeting immunosuppressive TAMs can improve responses to ICB in NB. We recently discovered that spleen tyrosine kinase (Syk) reprograms TAMs toward an immunostimulatory phenotype and enhances T-cell responses in the lung adenocarcinoma model. Here we investigated if Syk is an immune-oncology target in NB and tested whether a novel immunotherapeutic approach utilizing Syk inhibitor together with radiation and ICB could provide a durable anti-tumor immune response in an MYCN amplified murine model of NB.MethodsMyeloid Syk KO mice and syngeneic MYCN-amplified cell lines were used to elucidate the effect of myeloid Syk on the NB tumor microenvironment (TME). In addition, the effect of Syk inhibitor, R788, on anti-tumor immunity alone or in combination with anti-PDL1 mAb and radiation was also determined in murine NB models. The underlying mechanism of action of this novel therapeutic combination was also investigated.ResultsHerein, we report that Syk is a marker of NB-associated macrophages and plays a crucial role in promoting immunosuppression in the NB TME. We found that the blockade of Syk in NB-bearing mice markedly impairs tumor growth. This effect is facilitated by macrophages that become immunogenic in the absence of Syk, skewing the suppressive TME towards immunostimulation and activating anti-tumor immune responses. Moreover, combining FDA-approved Syk inhibitor, R788 (fostamatinib) along with anti-PDL1 mAb provides a synergistic effect leading to complete tumor regression and durable anti-tumor immunity in mice bearing small tumors (50 mm3) but not larger tumors (250 mm3). However, combining radiation to R788 and anti-PDL1 mAb prolongs the survival of mice bearing large NB9464 tumors.ConclusionCollectively, our findings demonstrate the central role of macrophage Syk in NB progression and demonstrate that Syk blockade can "reeducate" TAMs towards immunostimulatory phenotype, leading to enhanced T cell responses. These findings further support the clinical evaluation of fostamatinib alone or with radiation and ICB, as a novel therapeutic intervention in neuroblastoma.
- Published
- 2023
42. Human Regulatory T Cells: Understanding the Role of Tregs in Select Autoimmune Skin Diseases and Post-Transplant Nonmelanoma Skin Cancers
- Author
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Oparaugo, Nicole Chizara, Ouyang, Kelsey, Nguyen, Nam Phuong N, Nelson, Amanda M, and Agak, George W
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Medicinal and Biomolecular Chemistry ,Chemical Sciences ,Microbiology ,Autoimmune Disease ,Transplantation ,Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Humans ,T-Lymphocytes ,Regulatory ,Autoimmune Diseases ,Autoimmunity ,Skin Neoplasms ,Skin Diseases ,Forkhead Transcription Factors ,T-regulatory cells ,autoimmunity ,T effector cells ,skin ,inflammation ,homeostasis ,immune suppression ,transplantation ,cancer ,Other Chemical Sciences ,Genetics ,Other Biological Sciences ,Chemical Physics ,Biochemistry and cell biology ,Medicinal and biomolecular chemistry - Abstract
Regulatory T cells (Tregs) play an important role in maintaining immune tolerance and homeostasis by modulating how the immune system is activated. Several studies have documented the critical role of Tregs in suppressing the functions of effector T cells and antigen-presenting cells. Under certain conditions, Tregs can lose their suppressive capability, leading to a compromised immune system. For example, mutations in the Treg transcription factor, Forkhead box P3 (FOXP3), can drive the development of autoimmune diseases in multiple organs within the body. Furthermore, mutations leading to a reduction in the numbers of Tregs or a change in their function facilitate autoimmunity, whereas an overabundance can inhibit anti-tumor and anti-pathogen immunity. This review discusses the characteristics of Tregs and their mechanism of action in select autoimmune skin diseases, transplantation, and skin cancer. We also examine the potential of Tregs-based cellular therapies in autoimmunity.
- Published
- 2023
43. Establishment of immune suppression by cancer cells in the tumor microenvironment
- Author
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Hiroyoshi NISHIKAWA
- Subjects
cancer immunotherapy ,immune checkpoint inhibitors ,tumor microenvironment ,immune suppression ,immune-genome precision medicine ,Science (General) ,Q1-390 - Abstract
With the clinical success of immune checkpoint inhibitors (ICIs), cancer immunotherapy has become an important pillar of cancer treatment in various types of cancer. However, more than half of patients fail to respond to ICIs, even in combination, uncovering a limited window of clinical responses. Therefore, it is essential to develop more effective cancer immunotherapies and to define biomarkers for stratifying responders and nonresponders by exploring the immunological landscape in the tumor microenvironment (TME). It has become clear that differences in immune responses in the TME determine the clinical efficacy of cancer immunotherapies. Additionally, gene alterations in cancer cells contribute to the development of the immunological landscape, particularly immune suppression in the TME. Therefore, integrated analyses of immunological and genomic assays are key for understanding diverse immune suppressive mechanisms in the TME. Developing novel strategies to control immune suppression in the TME from the perspective of immunology and the cancer genome is crucial for effective cancer immunotherapy (immune-genome precision medicine).
- Published
- 2024
- Full Text
- View/download PDF
44. Chlamydia trachomatis enhances HPV persistence through immune modulation
- Author
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Yingying Lu, Qi Wu, Li Wang, and Lingting Ji
- Subjects
Chlamydia trachomatis ,HPV ,Langerhans cell ,Pathway ,Immune suppression ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Chlamydia trachomatis (CT) is the most common sexually transmitted infections globally, and CT infection can enhance HPV persistence. Epidemiological analysis has shown that patients with CT/HPV coinfection have a higher risk of developing cervical cancer and exhibit more rapid progression to cervical cancer than patients with HPV infection alone. However, the mechanism has not been fully elucidated. Here, we report that CT infection supports HPV persistence by further suppressing the functions of Langerhans cells (LCs); in particular, CT further activates the PI3K pathway and inhibits the MAPK pathways in LCs, and these pathways are frequently involved in the regulation of immune responses. CT/HPV coinfection also impairs LC functions by reducing the antigen-presenting ability and density of LCs. Moreover, CT/HPV coinfection can alter T-cell subsets, resulting in fewer CD4 + and CD8 + T cells and more infiltrating Tregs. Moreover, CT/HPV coinfection decreases the CD4 + /CD8 + T cell ratio to below 1, coinfection also induces greater T lymphocytes’ apoptosis than HPV infection, thus impairing cell-mediated immunity and accelerating the progress to cervical cancer.
- Published
- 2024
- Full Text
- View/download PDF
45. Exosome regulation of immune response mechanism: Pros and cons in immunotherapy
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Julien Milon Essola, Mengjie Zhang, Haiyin Yang, Fangzhou Li, Bozhang Xia, Jacques François Mavoungou, Abid Hussain, and Yuanyu Huang
- Subjects
Exosome ,Immune activation ,Immune suppression ,Tumor cells ,RNAs ,Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Biology (General) ,QH301-705.5 - Abstract
Due to its multiple features, including the ability to orchestrate remote communication between different tissues, the exosomes are the extracellular vesicles arousing the highest interest in the scientific community. Their size, established as an average of 30–150 nm, allows them to be easily uptaken by most cells. According to the type of cells-derived exosomes, they may carry specific biomolecular cargoes used to reprogram the cells they are interacting with. In certain circumstances, exosomes stimulate the immune response by facilitating or amplifying the release of foreign antigens-killing cells, inflammatory factors, or antibodies (immune activation). Meanwhile, in other cases, they are efficiently used by malignant elements such as cancer cells to mislead the immune recognition mechanism, carrying and transferring their cancerous cargoes to distant healthy cells, thus contributing to antigenic invasion (immune suppression). Exosome dichotomic patterns upon immune system regulation present broad advantages in immunotherapy. Its perfect comprehension, from its early biogenesis to its specific interaction with recipient cells, will promote a significant enhancement of immunotherapy employing molecular biology, nanomedicine, and nanotechnology.
- Published
- 2024
- Full Text
- View/download PDF
46. Chronic social defeat stress-induced depression reduces BCG efficacy by promoting regulatory T-cell levels in mice
- Author
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Rohit Tyagi, Xi Chen, Atika Dhar, Bing Yang, Wei Zhou, Aikebaier Reheman, Yingying Lei, and Gang Cao
- Subjects
BCG ,Vaccine efficacy ,Treg ,Immune suppression ,Depression ,Veterinary medicine ,SF600-1100 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Despite the initial successes of the Bacillus Calmette-Guerin (BCG) vaccine in children, its efficacy against tuberculosis is highly variable. There is a lack of understanding about how mental conditions influence BCG vaccination. Here, we used the chronic social defeat stress (CSDS) model to explore the effects of depression on BCG vaccination efficacy. We observed higher lung and spleen bacterial loads and a lower organ index in depressed compared to BCG mice. Meanwhile, a relatively lower T cell protective efficacy was observed in both compared to control and BCG mice via a mycobacterium growth inhibition assay (MGIA). Cytokine expression of IL-12p40, IL-1β, IL-17, TNF-α and IFN-γ was reduced, whereas the expression of IL-10 and IL-5 was increased in the spleen of both compared to BCG mice. Moreover, the proportions of CD4+IFN-γ+, CD8+IFN-γ+ T lymphocytes and CD4+ effector/central memory T cells were reduced in the splenocytes of the depressed BCG mice. Depression promotes CD4+ regulatory T cells (Treg) and myeloid-derived suppressor cell (MDSC) generation in depressed mice, contributing to the reduced pro-inflammatory immune response upon BCG vaccination. This study provides insight into the decreased protective immunity by BCG vaccination attributable to depression in mice.
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- 2023
- Full Text
- View/download PDF
47. Covid-19 Vaccine Response in Immunocompromised Haematology Patients (COVAC-IC)
- Author
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University Hospitals of North Midlands NHS Trust Charity and Staffordshire University
- Published
- 2023
48. Immun Status at Pancreatitis Patients
- Author
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Ufuk Oguz Idiz, Principal Investigator
- Published
- 2023
49. S100A8/A9 and Innate Immunity in Liver Disease
- Author
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King's College Hospital NHS Trust
- Published
- 2023
50. Chlamydia trachomatis enhances HPV persistence through immune modulation.
- Author
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Lu, Yingying, Wu, Qi, Wang, Li, and Ji, Lingting
- Subjects
- *
CHLAMYDIA trachomatis , *HUMAN papillomavirus , *IMMUNOREGULATION , *SEXUALLY transmitted diseases , *LANGERHANS cells - Abstract
Chlamydia trachomatis (CT) is the most common sexually transmitted infections globally, and CT infection can enhance HPV persistence. Epidemiological analysis has shown that patients with CT/HPV coinfection have a higher risk of developing cervical cancer and exhibit more rapid progression to cervical cancer than patients with HPV infection alone. However, the mechanism has not been fully elucidated. Here, we report that CT infection supports HPV persistence by further suppressing the functions of Langerhans cells (LCs); in particular, CT further activates the PI3K pathway and inhibits the MAPK pathways in LCs, and these pathways are frequently involved in the regulation of immune responses. CT/HPV coinfection also impairs LC functions by reducing the antigen-presenting ability and density of LCs. Moreover, CT/HPV coinfection can alter T-cell subsets, resulting in fewer CD4 + and CD8 + T cells and more infiltrating Tregs. Moreover, CT/HPV coinfection decreases the CD4 + /CD8 + T cell ratio to below 1, coinfection also induces greater T lymphocytes' apoptosis than HPV infection, thus impairing cell-mediated immunity and accelerating the progress to cervical cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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