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Cancer immunobiology is one of the hot topics of discussion amongst researchers today, and immunotherapeutic modalities are among the selected few emerging approaches to cancer treatment that have exhibited a promising outlook. However, immunotherapy is not a new kid on the block; it has been around for centuries. The origin of cancer immunotherapy in modern medicine can be traced back to the initial reports of spontaneous regression of malignant tumors in some patients following an acute febrile infection, at the turn of the twentieth century. This review briefly revisits the historical accounts of immunotherapy, highlighting some of the significant developments in the field of cancer immunobiology, that have been instrumental in bringing back the immunotherapeutic approaches to the forefront of cancer research. Some of the topics covered are: Coley's toxin—the first immunotherapeutic; the genesis of the theory of immune surveillance; the discovery of T lymphocytes and dendritic cells and their roles; the role of tumor antigens; relevance of tumor microenvironment; the anti-tumor (therapeutic) ability of Bacillus Calmette– Guérin; Melacine—the first therapeutic vaccine engineered; theories of immunoediting and immunophenotyping of cancer; and Provenge—the first FDA-approved therapeutic vaccine. In this review, head and neck cancer has been taken as the reference tumor for narrating the progression of cancer immunobiology, particularly for highlighting the advent of immunotherapeutic agents. [ABSTRACT FROM AUTHOR]

This mini review summarizes the immunobiology of myelodysplastic syndromes, specifically focusing on the interactions between immune cells, cytokines, and dysplastic cells within the tumor microenvironment in the bone marrow. We elucidate in detail how immune dysregulation and evasion influence the initiation and progression of myelodysplastic syndromes, as well as resistance to therapy and progression to AML. In addition, we highlight a range of therapeutic strategies, including the most recent breakthroughs and experimental therapies for treating MDS. Finally, we address the existing knowledge gaps in the understanding of the immunobiology of MDS and propose future research directions, promising advancements toward enhancing clinical outcomes and survival for patients with MDS. [ABSTRACT FROM AUTHOR]

Meningiomas are the most common primary intracranial tumors in adults and typically have a slow-growing and benign nature. However, there is also a substantial subset of meningiomas that shows aggressive clinical behavior and is refractory to standard treatment modalities, which are still limited to surgery and/or radiotherapy. Despite intensive research, no systemic treatment options are yet available in the clinic for these challenging tumors, resulting in poor patient outcome. Intensive research on the molecular pathogenesis of meningiomas has led to improved diagnostic tools, but so far there is no standardized implementation for the molecular profiling of these tumors for clinical practice. Recent research advances have also focused on the immunophenotyping of meningiomas, leading to several clinical trials examining the use of immune checkpoint blockade therapy in patients with clinically aggressive subtypes. In this review, we aim to summarize the current knowledge on the molecular and immunological landscape of meningiomas in detail and provide current and progressive ideas for future directions. [ABSTRACT FROM AUTHOR]

The 16th International Symposium on Schistosomiasis, held in Brazil, focused on disease control and elimination. Participants from 11 countries discussed various aspects of schistosomiasis, including the development of disease control tools and health education. The symposium featured keynote speeches, poster presentations, panel discussions, and abstract submissions. A Research Topic dedicated to the symposium aimed to disseminate selected studies presented during the event, covering topics such as diagnostic tests, host-parasite interactions, potential drug targets, and vaccine development. These studies contribute to the search for new strategies to combat schistosomiasis. The text also highlights the importance of education and diagnostic development in achieving the World Health Organization's guidelines for controlling and eliminating the disease. [Extracted from the article]

This mini review summarizes the immunobiology of myelodysplastic syndromes, specifically focusing on the interactions between immune cells, cytokines, and dysplastic cells within the tumor microenvironment in the bone marrow. We elucidate in detail how immune dysregulation and evasion influence the initiation and progression of myelodysplastic syndromes, as well as resistance to therapy and progression to AML. In addition, we highlight a range of therapeutic strategies, including the most recent breakthroughs and experimental therapies for treating MDS. Finally, we address the existing knowledge gaps in the understanding of the immunobiology of MDS and propose future research directions, promising advancements toward enhancing clinical outcomes and survival for patients with MDS.

Histopathologic lung allograft injuries are putative harbingers for chronic lung allograft dysfunction (CLAD). However, the mechanisms responsible are not well understood. CXCL9 and CXCL10 are potent chemoattractants of mononuclear cells and potential propagators of allograft injury. We hypothesized that these chemokines would be quantifiable in plasma, and would associate with subsequent CLAD development. In this prospective multicenter study, we evaluated 721 plasma samples for CXCL9/CXCL10 levels from 184 participants at the time of transbronchial biopsies during their first-year post-transplantation. We determined the association between plasma chemokines, histopathologic injury, and CLAD risk using Cox proportional hazards models. We also evaluated CXCL9/CXCL10 levels in bronchoalveolar lavage (BAL) fluid and compared plasma to BAL with respect to CLAD risk. Plasma CXCL9/CXCL10 levels were elevated during the injury patterns associated with CLAD, acute rejection, and acute lung injury, with a dose-response relationship between chemokine levels and CLAD risk. Importantly, there were strong interactions between injury and plasma CXCL9/CXCL10, where histopathologic injury associated with CLAD only in the presence of elevated plasma chemokines. We observed similar associations and interactions with BAL CXCL9/CXCL10 levels. Elevated plasma CXCL9/CXCL10 during allograft injury may contribute to CLAD pathogenesis and has potential as a minimally invasive immune monitoring biomarker.

It is easy to feel as if you are alone in academia, especially if you face challenges that not everyone does, or can, understand. Community is essential in facing these challenges, and we each have a role to play in creating a more equitable research community. Here, I discuss the importance of community, finding your village and being part of the academic support system. [ABSTRACT FROM AUTHOR]

B-cell targeted therapies, including anti-CD20 monoclonal antibodies (mAb) and Bruton’s tyrosine kinase inhibitors (BTKi), further suppress antibody (Ab) response to vaccines in patients with chronic lymphocytic leukemia (CLL). We conducted a prospective cohort study of SARS-CoV-2 vaccination in 81 CLL patients receiving BTKi (n=54), venetoclax (VEN, n=9), or who were treatment naïve (TN, n=18). Anti-spike Ab were detected in 53% of patients on BTKi post-primary series and 84% post-booster, 57% of patients on VEN post-primary series and 50% post-booster, and 67% of TN patients post-primary series and 87% post-booster. T-cell response to the primary series was independent of Ab response. At the time of booster, 12 patients interrupted BTKi (median 21d, range 8–22) and 33 continued BTKi. Among patients with detectable Ab post-booster, those who interrupted BTKi (n=10) had significantly higher Ab titers (median 7149 units/mL) compared with patients who continued BTKi (n=27, median 2071 units/mL, p = .04). [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) defined as a small fraction of cells within malignancies have been isolated from tumors with different histological origins with stem related characteristics such as self-replicating potential, tumorigenesis, and therapy resistance. The dynamic communication between CSCs and tumor microenvironment particularly immune cells orchestrates their fate and plasticity as well as the patient outcome. According to recent evidence, it has been reported that they harness different immunological pathways to escape immunosurveillance and express aberrantly immunomodulatory agents or decreased levels of factors forming antigen presenting machinery (APM), subsequently followed by impaired antigen presentation and suppressed immune detection. As effective therapies are expected to be able to eradicate CSCs, mechanistic understanding of such interactions can provide insights into causes of therapy failure particularly in immunotherapy. Also, it can contribute to enhance the practical interventions against CSCs and their immunomodulatory features resulting in CSCs eradication and improving patient clinical outcome. The aim of this review is to explain the present knowledge regarding the immunobiology of CSCs and the immunoevasion mechanisms they use. [ABSTRACT FROM AUTHOR]

Summary: The addition of interferon to tyrosine kinase inhibitors (TKIs), to improve deep molecular response (DMR) and potentially treatment‐free remission (TFR) rates in chronic‐phase chronic myeloid leukaemia (CP‐CML) patients is under active investigation. However, the immunobiology of this combination is poorly understood. We performed a comprehensive longitudinal assessment of immunological changes in CML patients treated with nilotinib and interferon‐alpha (IFN‐α) within the ALLG CML11 trial (n = 12) or nilotinib alone (n = 17). We demonstrate that nilotinib+IFN transiently reduced absolute counts of natural killer (NK) cells, compared with nilotinib alone. Furthermore, CD16+‐cytolytic and CD57+CD62L−‐mature NK cells were transiently reduced during IFN therapy, without affecting NK‐cell function. IFN transiently increased cytotoxic T‐lymphocyte (CTL) responses to leukaemia‐associated antigens (LAAs) proteinase‐3, BMI‐1 and PRAME; and had no effect on regulatory T cells, or myeloid‐derived suppressor cells. Patients on nilotinib+IFN who achieved MR4.5 by 12 months had a significantly higher proportion of NK cells expressing NKp46, NKp30 and NKG2D compared with patients not achieving this milestone. This difference was not observed in the nilotinib‐alone group. The addition of IFN to nilotinib drives an increase in NK‐activating receptors, CTLs responding to LAAs and results in transient immune modulation, which may influence earlier DMR, and its effect on long‐term outcomes warrants further investigation. [ABSTRACT FROM AUTHOR]

Amphibians are cold-blooded vertebrates that serve as a bridge between aquatic life and terrestrial life with more than 8000 species in the world, divided into 3 orders: Anura, Urodela and Gymnophiona. In addition, they have been the subject of many studies due to their cosmopolitan structure, easy culturing, amplification and potential clinical applications. The mature eggs of most animal species are surrounded by extracellular layers or structures such as vitelline membrane, jelly, and zona pellucida. Amphibian eggs are bordered by a vitelline envelope of these structures and several jelly layers that are structurally and chemically different. These layers are characteristic feature of amphibian eggs and are described as a gelatinous matrix that is insoluble in water. These jelly layers, which look quite simple from the outside, protect the embryo against harsh environmental conditions in nature, nourish it, and allow it to grow and develop. The information in the literature on amphibian egg jelly, which plays such an important role, is very limited. In this review, the morphological structure, content, effect on fertilization and immunobiological activity of amphibian egg jelly are discussed. [ABSTRACT FROM AUTHOR]

The course group of immunobiology for undergraduates of University of Science and Technology of China is a teaching system established by combining the characteristics of Biology and Medical Immunology. The course group pays attention to the cultivation of students' correct values and scientific research spirit, and has established a "Three Echelon" overall course teaching system of immunobiology with logical relationship. At the same time, it organically combines the course teaching with scientific research practice and scientific research integrity education, pays attention to transforming clinical issues into scientific questions, so as to motivating students' innovative thinking, improving students' comprehensive ability to solve problems, promoting the intersection and integration of biology and medical immunology. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Multifactorial interaction among various susceptible factors such as environmental, hormonal, and genetic factors makes it more heterogeneous and complex. Genetic and epigenetic modifications have been realized to regulate the immunobiology of lupus through environmental modifications such as diet and nutrition. Although these interactions may vary from population to population, the understanding of these risk factors can enhance the perception of the mechanistic basis of lupus etiology. To recognize the recent advances in lupus, an electronic search was conducted among search engines such as Google Scholar and PubMed, where we found about 30.4% publications of total studies related to genetics and epigenetics, 33.5% publications related to immunobiology and 34% related to environmental factors. These outcomes suggested that management of diet and lifestyle have a direct relationship with the severity of lupus that influence via modulating the complex interaction among genetics and immunobiology. The present review emphasizes the knowledge about the multifactorial interactions between various susceptible factors based on recent advances that will further update the understanding of mechanisms involved in disease pathoetiology. Knowledge of these mechanisms will further assist in the creation of novel diagnostic and therapeutic options. [ABSTRACT FROM AUTHOR]

Gestational trophoblastic diseases are a heterogeneous group of pregnancy related tumors that show extensive metastatic spread but are readily responsive to chemotherapy. This one of a kind treatability of gestational trophoblastic tumors may to some extent be inferable from a host immunologic reaction to the paternal antigens that are expressed on the trophoblastic cells. In this review, we evaluate the current cognizance of immunobiology of gestational trophoblastic diseases and also establish the immunologic behaviour of gestational trophoblastic diseases which should be researched further in order to gain a better understanding of the aetiology of these neoplasias. This will further help structuring immunotherapeutic methodologies for their treatment.

Dendritic cell (DC)-based cancer vaccines are a form of immunotherapy that activates the innate and adaptive immune systems to combat cancers. Neutrophils contribute to cancer biology and have the potential to be exploited by immunotherapeutic platforms to enhance anti-tumor immune responses. We previously showed that DC vaccines elicit the expansion of mouse interferon (IFN)γ-producing mature natural killer (NK) cells to elevate anti-tumor responses. Here, we demonstrate the rapid recruitment of neutrophils to the draining lymph nodes of DC-vaccinated mice. This was accompanied by an increase in the total number of NK cells producing IFN γ and expressing CD107a, a marker of degranulation that demonstrates NK cell functional activity. Furthermore, the depletion of neutrophils in DC-immunized mice resulted in decreased numbers of NK cells in draining lymph nodes compared to the controls. Interestingly, the increased number of IFNγ- and CD107a-expressing NK cells in DC-immunized mice was not detected in mice depleted of neutrophils. Further investigations showed that DC vaccines induced IFN γ − and TNF α -producing CD8+ T cells that also expressed CD107a, but depletion of neutrophils did not have any impact on the CD8+ T cell population. Our findings suggest that neutrophil-mediated anti-tumor immunity induced by a DC vaccine platform could be targeted to provide innovative strategies to enhance its clinical efficacy. [ABSTRACT FROM AUTHOR]

Purpose: The immune system’s role in mediating the cytotoxic effects of chemoradiotherapy remains not completely understood. The integration of immunotherapies into treatment will require insight into features and timing of the immune microenvironment associated with treatment response. Here, we investigated the role of circulating neutrophils and tumor-associated myeloid cells (TSAMs) as potential agents and biomarkers for disease-related outcomes in locally advanced cervical cancer (LACC). Material and Methods: Hematologic parameters for two LACC patient cohorts, a retrospective clinical and a prospective translational cohort, were obtained at baseline, weekly during chemoradiotherapy for the retrospective cohort, biweekly during chemoradiotherapy for the prospective cohort, and at the first follow-up visit for both cohorts (mean 14.7 weeks, range 8.1–25.1 weeks for the prospective cohort and 5.3 weeks with a range of 2.7–9.0 weeks for the retrospective cohort). In both cohorts, baseline as well as mean and lowest on-treatment values for platelets, hemoglobin, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) were analyzed for correlations with disease-related outcomes. In the prospective cohort, circulating myeloid cells were isolated from peripheral blood mononuclear cells (PBMCs), and TSAMs were isolated from tumor tissue via a novel serial cytobrush sampling assay. The samples were analyzed by flow cytometry. Results: In both cohorts, the only hematologic parameter significantly associated with survival was elevated on-treatment mean ANC (mANC), which was associated with lower local failure-free and overall survival rates in the retrospective and prospective cohorts, respectively. mANC was not associated with a difference in distant metastases. CD11b+CD11c- TSAMs, which act as a surrogate marker for intratumoral neutrophils, steadily decreased during the course of chemoRT and nadier’d at week 5 of treatment. Conversely, circulating myeloid cells identified from PBMCs steadily increased through week 5 of treatment. Regression analysis confirmed an inverse relationship between circulating myeloid cells and TSAMs at this time point. Conclusions: These findings identify on-treatment mean neutrophil count as a predictor of disease-related outcomes, suggest that neutrophils contribute to chemoradiation treatment resistance, and demonstrate the importance of techniques to measure intratumoral immune activity.

Microsatellite-instability-high (MSI-H) cancers form a spectrum of solid organ tumors collectively known as Lynch Syndrome cancers, occurring not only in a subset of colorectal, endometrial, small bowel, gastric, pancreatic, and biliary tract cancers but also in prostate, breast, bladder, and thyroid cancers. Patients with Lynch Syndrome harbor germline mutations in mismatch repair genes, with a high degree of genomic instability, leading to somatic hypermutations and, therefore, oncogenesis and cancer progression. MSI-H cancers have unique clinicopathological characteristics compared to their microsatellitestable (MSS) counterparts, marked by a higher neoantigen load, immune cell infiltration, and a marked clinical response to immune checkpoint blockade. Patients with known Lynch Syndrome may be detected early through surveillance, but some patients present with disseminated metastatic disease. The treatment landscape of MSI-H cancers, especially colorectal cancers, has undergone a paradigm shift and remains to be defined, with immune checkpoint blockade coming to the forefront of treatment strategies in the stage IV setting. We summarize in this review the clinical features of MSI-H cancers with a specific interest in the pattern of spread or recurrence, disease trajectory, and treatment strategies. We also summarize the tumor-immune landscape and genomic profile of MSI-H cancers and potential novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Ewing sarcoma is a fusion-oncoprotein-driven primary bone tumor most commonly diagnosed in adolescents. Given the continued poor outcomes for patients with metastatic and relapsed Ewing sarcoma, testing innovative therapeutic approaches is essential. Ewing sarcoma has been categorized as a ‘BRCAness’ tumor with emerging data characterizing a spectrum of DNA damage repair defects within individual Ewing tumors, including the presence of EWSR1::FLI1 itself, recurrent somatic mutations, and rare germline-based defects. It is critical to understand the cumulative impact of various DNA damage repair defects on an individual Ewing tumor’s response to therapy. Further, in addition to DNA-damage-directed therapies, subsets of Ewing tumors may be more susceptible to DNA-damage/immunotherapy combinations given the significant cross-talk between DNA damage and inflammatory pathways in the tumor microenvironment. Here we review potential approaches utilizing DNA-damaging agents as modulators of the Ewing tumor immune microenvironment, with a focus on radiation and opportunities during disease metastasis and relapse.

The IL-33/ST2 axis is reported to be controversially associated with coronary artery disease (CAD). A systematic review of the association between the IL-33/ST2 axis and CAD revealed that IL-33/ST2 plays a protective role in CAD and serum sST2 and IL-33 levels are increased in patients with cardiovascular disease. Therefore, the association of IL-33/ST2 single nucleotide polymorphisms (SNPs) with CAD prevalence, prognosis, and risk factors was assessed by performing a meta-analysis. Through a literature search of relevant articles in various databases using the relevant keywords, seven studies were included in the analysis. The meta-analysis showed that the IL-33/ST2 axis was associated with increased CAD risk [pooled odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.13–1.20]. Gene subgroup analysis showed a close association of IL1RL1 (OR = 1.25, 95% CI: 1.20–1.30; I2 = 85.9%; p = 0.000) and IL1RAcP (OR = 1.42, 95% CI: 1.26–1.60; I2 = 27.1%; p = 0.203) with increased CAD risk. However, the association for the IL-33 gene was not statistically significant. SNPs rs7044343 (T), rs10435816 (G), rs11792633 (C) in IL-33 gene were associated with a protective effect in CAD. However, rs7025417 (T) in IL-33, rs11685424 (G) in IL1RL1, rs950880 (A) in sST2, and rs4624606 (A) in IL1RAcP were related to increased CAD risk. Overall, polymorphisms in IL-33/ST2 axis components were associated with increased CAD risk. These results may help identify key features of IL-33/ST2 immunobiology in CAD along with potential treatment strategies to lower disease burden.

Achieving fast immunosuppression blood exposure after kidney transplantation is key to abrogating both preformed and de novo anti-donor humoral and cellular alloresponses. However, while tacrolimus (TAC) is the cornerstone immunosuppressant inhibiting adaptive alloimmunity, its blood exposure is directly impacted by different single-nucleotide polymorphisms (SNPs) in CYP3A TAC-metabolizing enzymes. Here, we investigated how functional TAC-CYP3A genetic variants (CYP3A4*22 / CYP3A5*3) influence the main baseline clinical and immunological risk factors of biopsy-proven acute rejection (BPAR) by means of preformed donor-specific antibodies (DSAs) and donor-specific alloreactive T cells (DSTs) in a large European cohort of 447 kidney transplants receiving TAC-based immunosuppression. A total of 70 (15.7%) patients developed BPAR. Preformed DSAs and DSTs were observed in 12 (2.7%) and 227 (50.8%) patients, respectively. According to the different CYP3A4*22 and CYP3A5*3 functional allele variants, we found 4 differential new clusters impacting fasting TAC exposure after transplantation; 7 (1.6%) were classified as high metabolizers 1 (HM1), 71 (15.9%) as HM2, 324 (72.5%) as intermediate (IM), and 45 (10.1%) as poor metabolizers (PM1). HM1/2 showed significantly lower TAC trough levels and higher dose requirements than IM and PM (p < 0.001) and more frequently showed TAC underexposure (<5 ng/ml). Multivariate Cox regression analyses revealed that CYP3A HM1 and IM pharmacogenetic phenotypes (hazard ratio (HR) 12.566, 95% CI 1.99–79.36, p = 0.007, and HR 4.532, 95% CI 1.10–18.60, p = 0.036, respectively), preformed DSTs (HR 3.482, 95% CI 1.99–6.08, p < 0.001), DSAs (HR 4.421, 95% CI 1.63–11.98, p = 0.003), and delayed graft function (DGF) (HR 2.023, 95% CI 1.22–3.36, p = 0.006) independently predicted BPAR. Notably, a significant interaction between T-cell depletion and TAC underexposure was observed, showing a reduction of the BPAR risk (HR 0.264, 95% CI 0.08–0.92, p = 0.037). Such variables except for DSAs displayed a higher predictive risk for the development of T cell-mediated rejection (TCMR). Refinement of pretransplant monitoring by incorporating TAC CYP3A SNPs with preformed DSAs as well as DSTs may improve current rejection-risk stratification and help induction treatment decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer (PC) is one of the main types of cancer that affects the male population worldwide. In recent decades, there has been a significant evolution in the methods of diagnosis and treatment, mainly due to the development of new research in the field of molecular biology, allowing for a better understanding of how this cancer develops and progresses from a genetic point of view. In addition to humans, the canine is the only mammal that develops PC spontaneously. However, in dogs, PC has a distinct form, with high lethality rates. This work of scientific characterization of cancer in humans and dogs approaches how differences and similarities already all explain how PC develops and progresses in dogs, with a central tenet of molecular biology, that is, the transport between DNA, RNA and proteins. The understanding of these mechanisms makes it possible to identify new methods of the diagnosis and treatment of the disease, not only in men, but also in dogs. First described in 1817, prostate cancer is considered a complex neoplastic entity, and one of the main causes of death in men in the western world. In dogs, prostatic carcinoma (PC) exhibits undifferentiated morphology with different phenotypes, is hormonally independent of aggressive character, and has high rates of metastasis to different organs. Although in humans, the risk factors for tumor development are known, in dogs, this scenario is still unclear, especially regarding castration. Therefore, with the advent of molecular biology, studies were and are carried out with the aim of identifying the main molecular mechanisms and signaling pathways involved in the carcinogenesis and progression of canine PC, aiming to identify potential biomarkers for diagnosis, prognosis, and targeted treatment. However, there are extensive gaps to be filled, especially when considering the dog as experimental model for the study of this neoplasm in humans. Thus, due to the complexity of the subject, the objective of this review is to present the main pathobiological aspects of canine PC from a comparative point of view to the same neoplasm in the human species, addressing the historical context and current understanding in the scientific field. [ABSTRACT FROM AUTHOR]

Achieving fast immunosuppression blood exposure after kidney transplantation is key to abrogating both preformed and de novo anti-donor humoral and cellular alloresponses. However, while tacrolimus (TAC) is the cornerstone immunosuppressant inhibiting adaptive alloimmunity, its blood exposure is directly impacted by different single-nucleotide polymorphisms (SNPs) in CYP3A TAC-metabolizing enzymes. Here, we investigated how functional TAC-CYP3A genetic variants (CYP3A4*22/CYP3A5*3) influence the main baseline clinical and immunological risk factors of biopsy-proven acute rejection (BPAR) by means of preformed donor-specific antibodies (DSAs) and donor-specific alloreactive T cells (DSTs) in a large European cohort of 447 kidney transplants receiving TAC-based immunosuppression. A total of 70 (15.7%) patients developed BPAR. Preformed DSAs and DSTs were observed in 12 (2.7%) and 227 (50.8%) patients, respectively. According to the different CYP3A4*22 and CYP3A5*3 functional allele variants, we found 4 differential new clusters impacting fasting TAC exposure after transplantation; 7 (1.6%) were classified as high metabolizers 1 (HM1), 71 (15.9%) as HM2, 324 (72.5%) as intermediate (IM), and 45 (10.1%) as poor metabolizers (PM1). HM1/2 showed significantly lower TAC trough levels and higher dose requirements than IM and PM (p < 0.001) and more frequently showed TAC underexposure (

Chronic lung allograft dysfunction (CLAD) remains one of the major limitations to long-term survival after lung transplantation. We modified a murine model of CLAD and transplanted left lungs from BALB/c donors into B6 recipients that were treated with intermittent cyclosporine and methylprednisolone postoperatively. In this model, the lung allograft developed acute cellular rejection on day 15 which, by day 30 after transplantation, progressed to severe pleural and peribronchovascular fibrosis, reminiscent of changes observed in restrictive allograft syndrome. Lung transplantation into splenectomized B6 alymphoplastic (aly/aly) or splenectomized B6 lymphotoxin-β receptor-deficient mice demonstrated that recipient secondary lymphoid organs, such as spleen and lymph nodes, are necessary for progression from acute cellular rejection to allograft fibrosis in this model. Our work uncovered a critical role for recipient secondary lymphoid organs in the development of CLAD after pulmonary transplantation and may provide mechanistic insights into the pathogenesis of this complication., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Ascariasis, caused by both Ascaris lumbricoides and Ascaris suum, is the most prevalent parasitic disease worldwide, affecting both human and porcine populations. However, due to the difficulties of assessing the early events of infection in humans, most studies of human ascariasis have been restricted to the chronic intestinal phase. Therefore, the Ascaris mouse model has become a fundamental tool for investigating the immunobiology and pathogenesis of the early infection stage referred to as larval ascariasis because of the model's practicality and ability to replicate the natural processes involved. The Ascaris mouse model has been widely used to explore factors such as infection resistance/susceptibility, liver inflammation, lung immune-mediated pathology, and co-infections and, notably, as a pivotal element in preclinical vaccine trials. Exploring the immunobiology of larval ascariasis may offer new insights into disease development and provide a substantial understanding of key components that trigger a protective immune response. This article focuses on creating a comprehensive guide for conducting Ascaris experimental infections in the laboratory as a foundation for future research efforts. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Acquisition and embryonation of Ascaris suum eggs from adult females Alternate Protocol: Cleaning and purification of Ascaris suum from female A. suum uteri Basic Protocol 2: Preparation of Ascaris suum eggs and murine infection Basic Protocol 3: Measurement of larval burden and Ascaris-larva-induced pathogenesis Basic Protocol 4: In vitro hatching and purification of Ascaris L3 larvae Support Protocol: Preparation of crude antigen from Ascaris infectious stages Basic Protocol 5: Ultrastructure-expansion microscopy (U-ExM) of Ascaris suum larval stages., (© 2024 Wiley Periodicals LLC.)