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A two‐dimensional tumor‐immune model with the time delay of the adaptive immune response is considered in this paper. The model is designed to account for the interaction between cytotoxic T lymphocytes (CTLs) and cancer cells on the surface of a solid tumor. The model considers the surface growth as a major growth pattern of solid tumors in order to describe the existence of necrotic kernels. The qualitative analysis shows that the immune‐free equilibrium is unstable, and the behavior of positive equilibrium is closely related to the ratio of the immune killing rate to tumor volume growth rate. The positive equilibrium is locally asymptotically stable when the ratio is smaller than a critical value. Otherwise, the occurrence of the delay‐driven Hopf bifurcation at the positive equilibrium is proved. Applying the center manifold reduction and normal form method, we obtain explicit formulas to determine the properties of the Hopf bifurcation. The global continuation of a local Hopf bifurcation is investigated based on the coincidence degree theory. The results reveal that the time of the adaptive immune system taken to response to tumors can lead to oscillation dynamics. We also carry out detailed numerical analysis for parameters and numerical simulations to illustrate our qualitative analysis. Numerically, we find that shorter immune response time can lead to longer patient survival time, and the period and amplitude of a stable periodic solution increase with the increasing immune response time. When CTLs recruitment rate and death rate vary, we show how the ratio of the immune killing rate to tumor volume growth rate and the first bifurcation value change numerically, which yields further insights to the tumor‐immune dynamics. [ABSTRACT FROM AUTHOR]

Tim-3 is a transmembrane protein that is highly expressed on subsets of chronically stimulated CD4+ helper and CD8+ cytotoxic T cells, with more transient expression during acute activation and infection. Tim-3 is also constitutively expressed by multiple types of myeloid cells. Like other TIM family members, Tim-3 can bind to phosphatidylserine displayed by apoptotic cells, and this interaction has been shown to mediate uptake of such cells by dendritic cells and cross-presentation of antigens to CD8+ T cells. In contrast, how the recognition of PS by Tim-3 might regulate the function of Tim- 3+ T cells is not known. In their recent paper, Lemmon and colleagues demonstrate for the first time that recognition of PS by Tim-3 leads to enhanced T cell activation. [ABSTRACT FROM AUTHOR]

Leukocyte extravasation into inflamed tissue is a complex process that is difficult to capture as a whole in vitro. We employed a bloodvessel- on-a-chip model in which human endothelial cells were cultured in a tube-like lumen in a collagen-1 matrix. The vessels are leak tight, creating a barrier for molecules and leukocytes. Addition of inflammatory cytokine TNF-α (also known as TNF) caused vasoconstriction, actin remodelling and upregulation of ICAM-1. Introducing leukocytes into the vessels allowed real-time visualization of all different steps of the leukocyte transmigration cascade, including migration into the extracellular matrix. Individual cell tracking over time distinguished striking differences in migratory behaviour between T-cells and neutrophils. Neutrophils cross the endothelial layer more efficiently than T-cells, but, upon entering the matrix, neutrophils display high speed but low persistence, whereas T-cells migrate with low speed and rather linear migration. In conclusion, 3D imaging in real time of leukocyte extravasation in a vessel-on-a-chip enables detailed qualitative and quantitative analysis of different stages of the full leukocyte extravasation process in a single assay. This article has an associated First Person interview with the first authors of the paper. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) which are more severe when ICIs are used in combination. We aimed to use a mouse model to elucidate the molecular mechanisms of immune-related hepatitis, one of the common irAEs associated with ICIs. Immune phenotyping and molecular profiling were performed on Pdcd1 -/- mice treated with anti-CTLA4 and/or the IDO1 inhibitor epacadostat or a 4-1BB agonistic antibody. ICI combination-induced hepatitis and 4-1BB agonist-mediated hepatitis share similar features yet maintain distinct immune signatures. Both were characterized by an expansion of periportal infiltrates and pan-zonal inflammation albeit with different morphologic characteristics. In both cases, infiltrates were predominantly CD4+ and CD8+ T cells with upregulated T-cell activation markers, ICOS and CD44. Depletion of CD8+ T cells abolished ICI-mediated hepatitis. Single-cell transcriptomics revealed that the hepatitis induced by combination ICIs is associated with a robust immune activation signature in all subtypes of T cells and T helper 1 skewing. Expression profiling revealed a central role for IFNγ and liver monocyte-derived macrophages in promoting a pro-inflammatory T-cell response to ICI combination and 4-1BB agonism. We developed a novel mouse model which offers significant value in yielding deeper mechanistic insight into immune-mediated liver toxicity associated with various immunotherapies. Hepatitis is one of the common immune-related adverse events in cancer patients receiving immune checkpoint inhibitor (ICI) therapy. The mechanisms of ICI-induced hepatitis are not well understood. In this paper, we identify key molecular mechanisms mediating immune intracellular crosstalk between liver T cells and macrophages in response to ICI in a mouse model. [Display omitted] • P dcd 1 -/- mouse can be utilized as a model for immune checkpoint inhibitor-mediated liver injury. • Single-cell immune transcriptional profiling revealed a landscape of molecular pathways responding to inhibition of PD1, CTLA4 and IDO1. • We identified a subset-specific T cell activation signature and common IFNγ signature. • Monocyte-derived macrophages coordinate the T cell response to immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Objective: To investigate clinical efficacy of pediatric massage combined with Xiaoer Xiaoji Zhike oral liquid and azithromycin in the treatment of children of mycoplasma pneumoniae pneumonia (MPP) and its effect on immune function and inflammatory factors. Methods: 80 cases of children with MPP who were treated in our hospital from March 2018 to June 2019 were selected. According to the different treatment methods, they were divided into the control group (azithromycin and Xiaoer Xiaoji Zhike oral liquid treatment, n=40) and the study group (pediatric massage, Xiaoer Xiaoji Zhike oral liquid, azithromycin treatment, n=40). The clinical efficacy of the two groups and the improvement of children's symptoms during the treatment were observed, peripheral blood T lymphocyte subsets, adverse reactions and serum inflammatory factors between the two groups were compared. Results: Compared with the control group, the clinical total effective rate of the study group was higher (P<0.05). Compared with the control group, the study group had a shorter of lung rales, cough and X-ray film of lung lesions to disappear time and antipyretic time (P<0.05). Compared with the control group, CD3+, CD4+ and CD4+/CD8+ in the study group was higher at 14 d after treatment, CD8+ was lower (P<0.05). Compared with the control group, interleukin-1β (IL-1β), C-reactive protein (CRP) and interleukin-6 (IL-6) in the study group were lower (P<0.05). There was no significant difference in incidence of adverse reactions in two groups (P>0.05). Conclusion: Pediatric massage combined with Xiaoer Xiaoji Zhike oral liquid and azithromycin in the treatment of children with MPP can promote the improvement of symptoms, optimize the clinical treatment effect, and effectively regulate the immune function and inflammatory factor levels of children. [ABSTRACT FROM AUTHOR]

The Astragalus membranaceus polysaccharide (APS4) with direct cytotoxicity on various cancer cells has been prepared in our previous study, while the underlying therapeutic role of APS4 on solid tumors in vivo hasn't been investigated yet. Therefore, in this paper, the lymphocytes-mediated antitumor and immunoregulatory activities of APS4 were researched by establishing S180 tumor-bearing mice model. Flow cytometry analysis revealed that APS4 could effectively regulate the percentages of CD3+, CD4+, CD8+ T cells and CD19+ B cells in thymus, peripheral blood and spleen of S180 tumor-bearing mice, dose-dependently. H&E staining and cell cycle determination of solid tumors manifested that APS4 treatment could significantly inhibit the growth of solid tumors by inducing cells apoptosis. Furthermore, two-dimensional electrophoresis and western blot analysis further demonstrated that APS4 could activate antitumor-related immune cells and promote anaerobic metabolism of tumor microenvironment, thereby causing the apoptosis of S180 tumor cells. These data implicated that APS4 could be used as a potential dietary supplement for immune enhancement. [ABSTRACT FROM AUTHOR]

Treatment failure or relapse due to tumor escape caused by reduction in target antigen expression has become a challenge in the field of CART therapy. Target antigen density is closely related to the effectiveness of CART therapy, and reduced or lost target antigen expression limits the efficacy of CART therapy and hinders the durability of CAR T cells. Epigenetic drugs can regulate histones for molecular modifications to regulate the transcriptional, translational and post-translational modification processes of target agents, and we demonstrated for the first time the role in regulating CD22 expression and its effect on the efficacy of CD22 CART. In this paper, we found that Chidamide promoted the expression of CD22 on the surface of B-cell tumor cells in vitro and in vivo, and enhanced the function of CD22 CART. As for mechanisms, we demonstrated that Chidamide did not affect CD22 mRNA transcription, but significantly increased the expression of total CD22 protein, indicating that Chidamide may upregulate cell surface CD22 expression by affecting the distribution of CD22 protein. In summary, our results suggest that Chidamide may enhance the efficacy of CD22 CART by inhibiting histone deacetylases to regulate post-transcriptional modifications that affect protein distribution to increase the expression of CD22 on the cell surface. [ABSTRACT FROM AUTHOR]

Motivation Identifying rare subpopulations of cells is a critical step in order to extract knowledge from single-cell expression data, especially when the available data is limited and rare subpopulations only contain a few cells. In this paper, we present a data mining method to identify small subpopulations of cells that present highly specific expression profiles. This objective is formalized as a constrained optimization problem that jointly identifies a small group of cells and a corresponding subset of specific genes. The proposed method extends the max-sum submatrix problem to yield genes that are, for instance, highly expressed inside a small number of cells, but have a low expression in the remaining ones. Results We show through controlled experiments on scRNA-seq data that the MicroCellClust method achieves a high F 1 score to identify rare subpopulations of artificially planted human T cells. The effectiveness of MicroCellClust is confirmed as it reveals a subpopulation of CD4 T cells with a specific phenotype from breast cancer samples, and a subpopulation linked to a specific stage in the cell cycle from breast cancer samples as well. Finally, three rare subpopulations in mouse embryonic stem cells are also identified with MicroCellClust. These results illustrate the proposed method outperforms typical alternatives at identifying small subsets of cells with highly specific expression profiles. Availabilityand implementation The R and Scala implementation of MicroCellClust is freely available on GitHub, at https://github.com/agerniers/MicroCellClust/ The data underlying this article are available on Zenodo, at https://dx.doi.org/10.5281/zenodo.4580332. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Mycosis fungoides (MF) is the most common subtype of primary cutaneous T cell lymphoma (CTCL). The erythrodermic form (T4) especially impairs health-related quality of life (HR-QoL), making patients often incapable of self-care. Mycosis fungoides and Sézary syndrome (SS) are immunogenic neoplasms and can be recognized by the patient's immune system. The disease is chronic and immunotherapy allows for long-term control of CTCL. The paper presents a description of 2 cases of nivolumab use in the salvage treatment of erythroderma in the course of refractory mycosis fungoides. Nivolumab was used as emergency treatment, and previously patients exhausted the available treatment options. The discussed cases confirm the effectiveness of immunotherapy in the treatment of primary cutaneous T cell lymphomas. The applied treatment achieved the effect of more than one year of response (15 months), as well as a significant benefit in terms of subjective and objective quality of life. The effect was mainly related to the condition of the skin. The use of the PD-1 checkpoint inhibitor allowed for over 12 months of control in advanced, refractory and heavily pretreated cutaneous lymphoma, and was very well tolerated. More research is needed on the use of such inhibitors in the treatment of cutaneous lymphomas. [ABSTRACT FROM AUTHOR]

In this essay, we show that 3 distinct approaches to immunological exhaustion coexist and that they only partially overlap, generating potential misunderstandings. Exploring cases ranging from viral infections to cancer, we propose that it is crucial, for experimental and therapeutic purposes, to clarify these approaches and their interconnections so as to make the concept of exhaustion genuinely operational. Author summary: In this essay, we have written a critical review on immunological exhaustion. We believe that this widely used concept often remains in fact imprecise because there exist 3 different approaches to exhaustion, namely, in terms of dysfunction, cause, and marker, and those are not sufficiently well distinguished and articulated in most scientific papers. We also propose to talk about "exhaustion" for and only for the phenomena in which all 3 approaches are aligned. This can be called the "convergence strategy": T cells would be described as "exhausted" if and only if they are simultaneously dysfunctional, express given markers such as programmed cell death protein 1 (PD-1), and induced by a specific cause such as chronicity. This strategy could be perfectly reasonable, and we see much value in adopting it, because it would force everyone to be more specific and rigorous when talking about exhaustion. Clarifying the characteristics of cells defined as "exhausted," and using a convergent strategy to define T-cell exhaustion could have major experimental and clinical consequences, including for viral infections such as the Coronavirus Disease 2019 (COVID-19). [ABSTRACT FROM AUTHOR]

Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can use the potency of the host immune system to fight against either solid or liquid cancers. Multiple myeloma (MM) or simply referred to as myeloma is a type of hematological malignancy that affects the plasma cells. The cancerous plasma cells produce immunoglobulins (antibodies) uncontrollably which consequently damage the tissues and organs and break the immune system function. Although the last few years have seen significant progressions in the treatment of MM, still a complete remission remains unconvincing. MM is a medically challenging and stubborn disease with a disappointingly low rate of survival rate. When comparing the three most occurring blood cancers (i.e., lymphoma, leukemia, and myeloma), myeloma has the lowest 5-year survival rate (around 40%). A low survival rate indicates a high mortality rate with difficulty in treatment. Therefore, novel CAR-T cell-based therapies or combination therapies along with CAT-T cells may bring new hope for multiple myeloma patients. CAR-T cell therapy has a high potential to improve the remission success rate in patients with MM. To date, many preclinical and clinical trial studies have been conducted to investigate the ability and capacity of CAR T cells in targeting the antigens on myeloma cells. Despite the problems and obstacles, CAR-T cell experiments in MM patients revealed a robust therapeutic potential. However, several factors might be considered during CAR-T cell therapy for better response and reduced side effects. Also, incorporating the CAT-T cell method into a combinational treatment schedule may be a promising approach. In this paper, with a greater emphasis on CAR-T cell application in the treatment of MM, we will discuss and introduce CAR-T cell's history and functions, their limitations, and the solutions to defeat the limitations and different types of modifications on CAR-T cells. [ABSTRACT FROM AUTHOR]

Immunological memory can be regarded as the key aspect of adaptive immunity, i.e. a specific response to first contact with an antigen, which in mammals is determined by the properties of T, B and NK cells. Re-exposure to the same antigen results in a more rapid response of the activated specific cells, which have a unique property that is the immunological memory acquired upon first contact with the antigen. Such a state of immune activity is also to be understood as related to "altered behavior of the immune system" due to genetic alterations, presumably maintained independently of the antigen. It also indicates a possible alternative mechanism of maintaining the immune state at a low level of the immune response, "directed" by an antigen or dependent on an antigen, associated with repeated exposure to the same antigen from time to time, as well as the concept of innate immune memory, associated with epigenetic reprogramming of myeloid cells, i.e. macrophages and NK cells. Studies on Teleostei have provided evidence for the presence of immunological memory determined by T and B cells and a secondary response stronger than the primary response. Research has also demonstrated that in these animals macrophages and NK-like cells (similar to mammalian NK cells) are able to respond when re-exposed to the same antigen. Regardless of previous reports on immunological memory in teleost fish, many reactions and mechanisms related to this ability require further investigation. The very nature of immunological memory and the activity of cells involved in this process, in particular macrophages and NK-like cells, need to be explained. This paper presents problems associated with adaptive and innate immune memory in teleost fish and characteristics of cells associated with this ability. • The presence of adaptive and innate immune memory has been confirmed in fish. • Adaptive immune memory in fish develops with the participation of T and B lymphocytes. • Innate immune memory is related to the properties of macrophages and NK-like cells. • There is a need to further verify the biological basis of this property. [ABSTRACT FROM AUTHOR]

Summary: Ageing dramatically affects number and function of both innate and adaptive arms of immune system, particularly T cell subsets, contributing to reduced vaccination efficacy, decreased resistance to infections and increased prevalence of cancer in older people. In the present paper, we analysed the age‐related changes in the absolute number of lymphocytes in 214 Sicilian subjects, and in the percentages of T and natural killer (NK) cells in a subcohort of donors. We compared these results with the immunophenotype of the oldest living Italian supercentenarian (aged 111 years). The results were also sorted by gender. The correlation between number/percentage of cells and age in all individuals. and separately in males and females, was examined using a simple linear regression analysis. We did not record the increase in the rate of inversion of the CD4/CD8 ratio, frequently reported as being associated with ageing in literature. Our observation was the direct consequence of a flat average trend of CD4+ and CD8+ T cell percentages in ageing donors, even when gender differences were included. Our results also suggest that CD4+ and CD8+ subsets are not affected equally by age comparing females with males, and we speculated that gender may affect the response to cytomegalovirus (CMV) infection. The supercentenarian showed a unique immunophenotypic signature regarding the relative percentages of her T cell subsets, with CD4+ and CD8+ T cell percentages and CD4+ naive T cell values in line with those recorded for the octogenarian subjects. This suggests that the supercentenarian has a naive 'younger' T cell profile comparable to that of a >80‐year‐old female. [ABSTRACT FROM AUTHOR]

We do not mention or discuss glucose intolerance in our study and regard Diabetes as a real disease and not glucose intolerance. The cohort described in the paper (cohort 1) is a part of Swedish population-based SCAPIS cohort containing more than 30 000 individuals. [Extracted from the article]

Clinicians are facing questions from some patients about speculative cell banking. Researchers recently published a paper intended to be a resource to prepare clinicians in all fields to discuss the limitations of gene cell therapy with their patients. They also hope they have created a resource for the general public. [ABSTRACT FROM AUTHOR]

In a recent paper, Schriek et al. show that, in a complement-dependent reaction, marginal zone B cells (MZBs) steal MHC class II (MHCII) from dendritic cells (DCs). Activation of T cells by stolen MHCII complexes potentially allows MZBs to augment or regulate T cell activation in ways that are distinct from DCs. [ABSTRACT FROM AUTHOR]

Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can use the potency of the host immune system to fight against either solid or liquid cancers. Multiple myeloma (MM) or simply referred to as myeloma is a type of hematological malignancy that affects the plasma cells. The cancerous plasma cells produce immunoglobulins (antibodies) uncontrollably which consequently damage the tissues and organs and break the immune system function. Although the last few years have seen significant progressions in the treatment of MM, still a complete remission remains unconvincing. MM is a medically challenging and stubborn disease with a disappointingly low rate of survival rate. When comparing the three most occurring blood cancers (i.e., lymphoma, leukemia, and myeloma), myeloma has the lowest 5-year survival rate (around 40%). A low survival rate indicates a high mortality rate with difficulty in treatment. Therefore, novel CAR-T cell-based therapies or combination therapies along with CAT-T cells may bring new hope for multiple myeloma patients. CAR-T cell therapy has a high potential to improve the remission success rate in patients with MM. To date, many preclinical and clinical trial studies have been conducted to investigate the ability and capacity of CAR T cells in targeting the antigens on myeloma cells. Despite the problems and obstacles, CAR-T cell experiments in MM patients revealed a robust therapeutic potential. However, several factors might be considered during CAR-T cell therapy for better response and reduced side effects. Also, incorporating the CAT-T cell method into a combinational treatment schedule may be a promising approach. In this paper, with a greater emphasis on CAR-T cell application in the treatment of MM, we will discuss and introduce CAR-T cell's history and functions, their limitations, and the solutions to defeat the limitations and different types of modifications on CAR-T cells. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses that infect the susceptible CD 4 + T cells. It is known that HIV and HTLV-I have in common a way of transmission through direct contact with certain body fluids related to infected individuals. Therefore, it is not surprising that a mono-infected person with one of these viruses can be co-infected with the other virus. In the literature, a great number of mathematical models has been presented to describe the within-host dynamics of HIV or HTLV-I mono-infection. However, the within-host dynamics of HIV/HTLV-I co-infection has not been modeled. In this paper, we develop a new within-host HIV/HTLV-I co-infection model. The model includes the impact of Cytotoxic T lymphocytes (CTLs) immune response, which is important to control the progression of viral co-infection. The model describes the interaction between susceptible CD 4 + T cells, silent HIV-infected cells, active HIV-infected cells, silent HTLV-infected cells, Tax-expressing HTLV-infected cells, free HIV particles, HIV-specific CTLs and HTLV-specific CTLs. We first show the nonnegativity and boundedness of the model's solutions and then we calculate all possible equilibria. We derive the threshold parameters which govern the existence and stability of all equilibria of the model. We prove the global asymptotic stability of all equilibria by utilizing Lyapunov function and LaSalle's invariance principle. We have presented numerical simulations to illustrate the effectiveness of our main results. In addition, we discuss the effect of HTLV-I infection on the HIV-infected patients and vice versa. [ABSTRACT FROM AUTHOR]

Interleukin-2 (IL-2) is a cytokine involved in the development and maturation of the subsets of T cells, critically associated with the progression of several immune-related diseases (e.g. liver disease, bowel disease). Interestingly, a recent study suggests that coffee may contain several compounds to inhibit IL-2 expression in activated T-lymphocytic cells. However, there is little information about the potential effects of several coffee compounds (e.g. kahweol, cafestol, trigonelline, niacin and chlorogenic acids) on IL-2 expression in activated T-lymphocytic cells. Therefore, in this paper, their effects on IL-2 expression were evaluated in PHA/PMA-activated lymphocytic Jurkat cells. Among the tested compounds, only kahweol and cafestol were able to reduce IL-2 production significantly in the cells (p < 0.05). However, the inhibition of kahweol was a bit stronger than cafestol. Therefore, the molecular mechanism underlying the IL-2 inhibition was investigated using kahweol. Kahweol (≤ 20 µM) was able to inhibit the phosphorylations of ERK and c-Fos (p < 0.05) with little effects on p38 and JNK phosphorylations in the Jurkat cells. Subsequently, the inhibition of ERK/c-Fos led to the reduction of IL-2 mRNA expression in the Jurkat cells. In summary, the data suggest that kahweol may be a potential coffee compound to reduce IL-2 production via inhibiting the phosphorylations of ERK/c-Fos in PHA/PMA-activated lymphocytic Jurkat cells. [ABSTRACT FROM AUTHOR]

With the success of immunosuppressive checkpoint in tumor therapy, the corresponding adverse response and drug resistance defects have been exposed. T cells and NK cells are the body's immune system of the two substantial main forces. in recent years, study of T cell checkpoints appeared a certain block, such as PD-1 the effect not benign, on the distribution of NK cell surface excitatory and inhibitory receptors under normal conditions to maintain steady, could be targeted in the tumor treatment blockade have therapeutic effect. This paper reviews the function of NK cells and the effects of corresponding receptors in various types of tumors, providing a direction for the selection of appropriate gate control sites for future treatment. [ABSTRACT FROM AUTHOR]

Early embryonic exogenous feeding of bioactive substances is a topic of interest in poultry production, potentially improving gastrointestinal tract (GIT) development, stimulating immunization, and maximizing the protection capability of newly hatched chicks. However, the biophysiological actions and effects of in ovo administered bioactive substances are inconsistent or not fully understood. Thus, this paper summarizes the functional effects of bioactive substances and their interaction merits to augment GIT development, the immune system, and microbial homeostasis in newly hatched chicks. Prebiotics, probiotics, and synbiotics are potential bioactive substances that have been administered in embryonic eggs. Their biological effects are enhanced by a variety of mechanisms, including the production of antimicrobial peptides and antibiotic responses, regulation of T lymphocyte numbers and immune-related genes in either up- or downregulation fashion, and enhancement of macrophage phagocytic capacity. These actions occur directly through the interaction with immune cell receptors, stimulation of endocytosis, and phagocytosis. The underlying mechanisms of bioactive substance activity are multifaceted, enhancing GIT development, and improving both the innate and adaptive immune systems. Thus summarizing these modes of action of prebiotics, probiotics and synbiotics can result in more informed decisions and also provides baseline for further research. [ABSTRACT FROM AUTHOR]

Summary: Prolonged cytopenia after CAR‐T cell therapy is an acknowledged problem. At present, the causes and implications of prolonged cytopenia are unclear. The paper by Kitamura et al identified that prolonged cytopenia is associated with alterations in the bone marrow niche identified before CAR‐T therapy, indicating a potential predictor of this serious side‐effect of treatment. Commentary on: Kitamura et al. Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T‐cell therapy? Br J Haematol 2023;202:294‐307. [ABSTRACT FROM AUTHOR]

Currently, immunomodulation is an alternative in the fight against many diseases, being considered a possibility to fight against many infectious diseases that can affect pig herds. Selenium can be used for this purpose, the effect of its administration on the immune response being the main purpose of the present study. Following the administration of organic selenium, we found that in the case of WBC parameters, granulocytes and agranulocytes percentages and lymphoblastic transformation percentages of B lymphocytes, there are no major differences between the values recorded at the beginning of the experiment and the values recorded in the two experimental moments. Instead, following the administration of organic selenium, we observed significant increases in T lymphocytes percentages (by 9.94%, after 21 days, and respectively by 8.18%, after 30 days), percentages of lymphoblastic transformation of T lymphocytes (by 59.59% after 21 days, and respectively by 64.14% after 30 days), as well as the helper T lymphocytes/supressor T lymphocytes ratio (by 46.15% after 21 days, and respectively by 65.38% after 30 days). Regarding the percentage of B lymphocytes, a decrease of this parameter is observed by 38.34% after 21 days and by 21.84% after 30 days following the administration of the product based on organic selenium. [ABSTRACT FROM AUTHOR]

The Th17/ Treg axis is a crucial regulator of anti-inflammatory and proinflammatory pathways that play fundamental roles in cancer and autoimmune diseases. The alteration of the Th17/Tregs axis is highly significant for developing novel therapeutic approaches. Th17 and Treg cells share a large portion of their transcriptome, albeit with distinct functions. The mechanisms governing the bifurcation of Th17 /Treg axis differentiation from naïve T cells are not yet understood. This study aims to identify the differentially expressed genes (DEGs) and gene-enriched pathways that contribute to the distinction between these closely aligned phenotypes. We analyzed RNA sequencing data of CD4+ T cells differentiated in vitro into Th0, Th17, and Tregs phenotypes and built gene enrichment networks. We studied the network rewiring of Th17 and Tregs from Th0 cells. In addition to common pathways and genes that are equally expressed between these two distinct phenotypes, we identified key genes and pathways that contribute to their distinctiveness. For example, the Keap1 gene and several of its interactors such as MCC1 were upregulated in Tregs indicating that Tregs possess mechanisms that prevent the over-activation of antioxidants pathways. Tregs also possess several genes that are involved in the hydrolysis of ATP to ADP as RAB37, ATP1A2, ATP1B, and PDE2A to ensure Treg anti-inflammatory capabilities. Additionally, one of the pathways that ensure Tregs differentiation and function seems to point toward an insulin role mediated by APOL9B and GOLM. Taken together our findings shed light on various essential regulators of the Th17/Treg axis and pave the way for treatment strategies that selectively target one phenotype while sparing the other. [ABSTRACT FROM AUTHOR]

Discrete tissue niches are emerging as essential prerequisites enabling cell communication and function in both homeostasis and disease. In a recent Cell paper, Di Pilato et al. identify a unique dendritic cell-cytotoxic T cell crosstalk within the perivascular space that facilitates T cell survival and proliferation and drives anti-tumor activity. [ABSTRACT FROM AUTHOR]

Objective: Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment for relapsed/refractory acute lymphoblastic leukemia (ALL) in pediatric oncology. However, little is known about the cognitive functioning of these patients. This study examines the neuropsychological functioning of pediatric patients referred for CAR T-cell therapy. Method: Data was obtained from a longitudinal observational study of CAR T-cell therapy patients (ages 1–30 years) at the Children's Hospital of Philadelphia. Neuropsychological data and neurotoxicity ratings were collected before and after CAR T-cell infusion, with brief cognitive testing at 28 days and 180 days post-infusion to assess acute changes. Cognitive testing included pencil-and-paper measures of intellectual functioning, attention, processing speed, and psychological functioning, as well as NIH Toolbox subtests. Results: Of 13 patients completing pre-infusion cognitive testing, 44% of patients scored below average (1 SD below the mean) on a timed visual-motor processing speed test. 20–25% of the sample scored below average on measures of executive functioning, attention/working memory, and expre0111111ssive vocabulary, exceeding what would be expected in a normal distribution. Fewer patients completed post-infusion assessments (n = 8, 28 days; n = 5, 6 months; n = 3, 1 year), with up to 50% scoring below average on the timed visual-motor processing speed test and 33% scoring below average on a measure of inhibitory control and selective attention after 1 year. Conclusions: Pediatric CAR T-cell therapy patients have high rates of cognitive dysfunction prior to receiving infusions, with evidence for increasing problems with timed visual-motor and executive functioning. Findings highlight the need to monitor pediatric CAR T-cell therapy patients throughout treatment. [ABSTRACT FROM AUTHOR]

• Docetaxel boosted anticancer effects of NK cells and CD8 + T lymphocytes. • Docetaxel stimulated the recruitment of tumor-associated macrophages. • Targeting some molecules such as PD-1 enhanced the anticancer activity of docetaxel. There are several interactions within the tumor microenvironment (TME) that affect the response of cancer cells to therapy. There are also a large number of cells and secretions in TME that increase resistance to therapy. Following the release of immunosuppressive, pro-angiogenic, and metastatic molecules by certain cells such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and cancer cells, immune evasion, angiogenesis, and metastasis may be induced. However, natural killer (NK) cells and cytotoxic CD8 + T lymphocytes (CTLs) can responsively release anticancer molecules. In addition, anticancer drugs can modulate these cells and their interactions in favor of either cancer resistance or therapy. Docetaxel belongs to taxanes, a class of anti-tumor drugs, which acts through the polymerization of tubulin and the induction of cell cycle arrest. Also, it has been revealed that taxanes including docetaxel affect cancer cells and the other cells within TME through some other mechanisms such as modulation of immune system responses, angiogenesis, and metastasis. In this paper, we explain the basic mechanisms of docetaxel interactions with malignant cells. Besides, we review the diverse effects of docetaxel on TME and cancer cells in consequence. Lastly, the modulatory effects of docetaxel alone or in conjunction with other anticancer agents on anti-tumor immunity, cancer cell resistance, angiogenesis, and metastasis will be discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • IDO1 induces immune tolerance within TME. • Serum profiling of IDO1 metabolites is of prognostic value. • IDO1 upregulation occurs after ICI therapy. • IDO1 inhibitors can be used safely with ICI therapy. • Epacadostat plus ICI renders promising clinical responses. • Clinical efficacy of anti-PD-L1/IDO inhibitor vaccination is promising. Metabolic alterations occur commonly in tumor cells as a way to adapt available energetic sources for their proliferation, survival and resistance. Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular enzyme catalyzing tryptophan degradation into kynurenine. IDO1 expression shows a rise in the stroma of many types of human cancers, and it provides a negative feedback mechanism for cancer evasion from immunosurveillance. Upregulation of IDO1 correlates with cancer aggression, poor prognosis and shortened patient survival. The increased activity of this endogenous checkpoint impairs effector T cell function, increases regulatory T cell (Treg) population and induces immune tolerance, so its inhibition potentiates anti-tumor immune responses and reshapes immunogenic state of tumor microenvironment (TME) presumably through normalizing effector T cell activity. A point is that the expression of this immunoregulatory marker is upregulated after immune checkpoint inhibitor (ICI) therapy, and that it has inducible effect on expression of other checkpoints. These are indicative of the importance of IDO1 as an attractive immunotherapeutic target and rationalizing combination of IDO1 inhibitors with ICI drugs in patients with advanced solid cancers. In this review, we aimed to discuss about the impact of IDO1 on tumor immune ecosystem, and the IDO1-mediated bypass of ICI therapy. The efficacy of IDO1 inhibitor therapy in combination with ICIs in advanced/metastatic solid tumors is also a focus of this paper. [ABSTRACT FROM AUTHOR]

Immunomodulation is an important alternative in combating many diseases, being considered a potential weapon in the fight against pathological entities that cause major economic losses in pig herds. Levamisole, in addition to its anthelmintic effect, has also an immunostimulatory effect, for which it has also been used as a vaccine adjuvant. The aim of the research was to evaluate the non-specific immune response in modern techniques in pigs given levamisole. The results showed significant differences in the case of the ratio of lymphocyte subpopulations, there was an increasing trend in favor of T lymphocytes (with 10.44%), and the % of T lymphocytes blastic transformation (with 56%). Also, we observed a significant increase of the LTh/LTs ratio (with 65.92%) which supports the immunomodulatory potential of the levamisole and its involvement on the coordination of immune processes. [ABSTRACT FROM AUTHOR]

Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease that is common in elderly people. Its classification in the spectrum of autoinflammatory and autoimmune diseases is difficult because of its only partially understood immune-mediated mechanisms. The literature concerning the innate and adaptive immune system activation in PMR was systematically reviewed highlighting the relative weight of autoinflammation and autoimmunity in its pathogenesis and disease progression. A literature search on PubMed Central and Embase scientific databases was performed by two independent reviewers. To be eligible, the studies needed to fully satisfy our initial PICO framework: a primary diagnosis of PMR as a population, the search for immune/inflammatory cells, cytokines and autoantibodies as an intervention, a control group consisting in healthy controls, patients with other inflammatory rheumatic diseases or PMR patients in remission after treatment and as outcomes the results of the investigations in the analyzed tissue samples. The most relevant data of the included papers were extracted by using a standardized template. Of the 933 screened abstracts, 52 papers were included in the systematic review and categorized depending on their primary research objectives. The hyper-activity of neutrophils and monocytes, expressing toll-like receptor 7 in active disease, an impaired phagocytosis and endothelial dysfunction, as well as an increased count of innate T cells in patients with remission emerged among the major derangements of the innate immune response in PMR. Among the cytokines profile, interleukin-6 plays a key role but other pro-inflammatory mediators and angiogenesis markers such as chemokines, B-cell activating factor, vascular endothelial growth factor and angiopoietins seem to be involved in refractory or glucocorticoid-resistant PMR. The aberrant adaptive immune response was documented by tissue and serum findings of polarized T cells towards T helper 1 and 17 phenotypes, an increased expression of immunosenescent surface markers and a downregulated immunoregulatory response. The altered distribution of peripheral B cells, detected during active disease, suggested their peripheral migration towards unidentified sites. The interaction between innate and adaptive immune response was documented by a synovial infiltrate of macrophages and T cells. Despite multiple autoantibodies have been detected in PMR patients, none proved to correlate with disease activity seeming to be reactive to the marked inflammation or antigenic determinants provided by environmental triggers or tissue/cell damage. The complex network between innate and adaptive immune system in PMR is supported by findings at molecular and cellular levels. By considering both the ends of the pathophysiological spectrum of immune-mediated rheumatic diseases, PMR may be regarded as an inflammatory immune-mediated disease with mixed mechanisms in a background of genetic and epigenetic factors together with immunological and endocrine senescence. • High concentrations of serum pro-inflammatory cytokines and cell growth factors identify active PMR patients • Innate immune cells might play a role both in PMR disease activity and sub-clinical ongoing inflammation. • T cells are dysregulated in PMR for a hyper-expression of immunosenescent markers and deficient immunoregulatory pathways. • B cells peripheral distribution is altered during active disease suggesting an inflammatory-driven compartmentalization. • Autoantibodies do not seem pathogenetic in PMR but may be reactive to external triggers or damaged tissues self-antigens. [ABSTRACT FROM AUTHOR]

• A model is proposed based on the key role of Regulatory T cells in chemoimmunotherapy. • The model's fixed points are obtained and the bifurcation diagrams are discussed. • New features of personalizing a cancer mathematical model are presented. • Considering Regulatory T cells leads to identifying critical patient conditions more precisely. Studying the mathematical dynamics of cancer has gained the attention of bioengineers in the past three decades. Different kinds of modelling considering various aspects of treatment have been proposed. In this paper, the key role of Regulatory T cells is discussed and a model in ordinary differential equation (ODE) form is proposed by adding this state to the system dynamics considering chemoimmunotherapy treatment. Regulatory T cells are considered as one of the main tumor cells' tactics to deceive the body's immune system. The improved model is verified mathematically and biologically and fits all criteria in both fields. The results show that entering Regulatory T cells state on cancer mathematical modelling for simulating body cells for chemoimmunotherapy provides a way to identify critical cases more carefully, which a simplified model is unable to accomplish. This point emphasizes the fact that this state must be present in cancer modelling to anticipate immune response more accurately. The advanced system fixed points are obtained by the Newton method and bifurcation diagrams are derived and discussed. New features and remarks are proposed during the journey of developing more accurate models that have the best fit with laboratory data. The sensitivity chart of the model is illustrated and novel aspects of discussions are made with the aim of personalizing a model for a patient and identifying critical conditions based on the chart before any treatment begins. This point enables physicians to determine whether critical conditions have occurred for a patient in a specific treatment or not. [ABSTRACT FROM AUTHOR]

[Display omitted] • SARS-CoV-2 promotes an inflammatory phenotype in human monocytes. • In SARS-CoV-2 stimulated PBMC Tα1 mitigates monocyte and myeloid DC activation. • Tα1 dampens SARS-CoV-2 mediated induction of pro-inflammatory cytokines. • Tα1 promotes release of the anti-inflammatory factors IL-10 from SARS-CoV- 2-stimulated PBMC. The peculiar property of Thymosin alpha 1 (Tα1) to act as master regulator of immune homeostasis has been successfully defined in different physiological and pathological contexts ranging from cancer to infection. Interestingly, recent papers also demonstrated its mitigating effect on the "cytokine storm" as well as on the T-cell exhaustion/activation in SARS-CoV-2 infected individuals. Nevertheless, in spite of the increasing knowledge on Tα1-induced effects on T cell response confirming the distinctive features of this multifaceted peptide, little is known on its effects on innate immunity during SARS-CoV-2 infection. Here, we interrogated peripheral blood mononuclear cell (PBMC) cultures stimulated with SARS-CoV-2 to disclose Tα1 properties on the main cell players of early response to infection, namely monocytes and myeloid dendritic cells (mDC). Moving from ex vivo data showing an enhancement in the frequency of inflammatory monocytes and activated mDC in COVID-19 patients, a PBMC-based experimental setting reproduced in vitro a similar profile with an increased percentage of CD16+ inflammatory monocytes and mDC expressing CD86 and HLA-DR activation markers in response to SARS-CoV-2 stimulation. Interestingly, the treatment of SARS-CoV-2-stimulated PBMC with Tα1 dampened the inflammatory/activation status of both monocytes and mDC by reducing the release of pro-inflammatory mediators, including TNF-α, IL-6 and IL-8, while promoting the production of the anti-inflammatory cytokine IL-10. This study further clarifies the working hypothesis on Tα1 mitigating action on COVID-19 inflammatory condition. Moreover, these evidence shed light on inflammatory pathways and cell types involved in acute SARS-CoV-2 infection and likely targetable by newly immune-regulating therapeutic approaches. [ABSTRACT FROM AUTHOR]

Created with BioRender.com [Display omitted] Cancer immunity is dependent on dynamic interactions between T cells and dendritic cells (DCs). Polymer-based nanoparticles target DC receptors to improve anticancer immune responses. In this paper, DC surface receptors and their specific coupling natural ligands and antibodies are reviewed and compared. Moreover, reaction mechanisms are described, and the synergistic effects of immune adjuvants are demonstrated. Also, extracellular-targeting antigen-delivery strategies and intracellular stimulus responses are reviewed to promote the rational design of polymer delivery systems. [ABSTRACT FROM AUTHOR]

Single event upset (SEU) is a critical issue for the static random access memory (SRAM) exposed to irradiated environments. In this paper, an area-efficient 6 T SRAM cell design based on partially depleted silicon-on-insulator (PDSOI) technology is proposed to improve the ability to resist SEU using tunnel-diode body-contact (TDBC) transistors. The proposed cell and 6 T floating body (FB) SOI SRAM cell are fabricated using 130 nm PDSOI technology for comparison purposes. Pulsed laser experiments show that, at the nominal supply voltage of 1.2 V, the energy threshold of the proposed cell increases by 25.2 % compared to the 6 T FB SOI cell with a similar area. The energy threshold of the traditional T-gate body-contact (TB) cell is also compared with that of the proposed cell. • An area-efficient 6 T SRAM cell design based on PDSOI technology is proposed to improve the ability of resisting SEU. • The proposed cell and 6 T floating body SOI SRAM cell are fabricated using 130 nm PDSOI technology for comparison purposes. • The energy threshold of the proposed cell increases by 25.2 % compared to the 6 T FB SOI cell with a similar area. [ABSTRACT FROM AUTHOR]

Malaria is a life-threatening disease caused by infection with Plasmodium parasites. The goal of developing an effective malaria vaccine is yet to be reached despite decades of massive research efforts. CD4+ helper T cells, CD8+ cytotoxic T cells, and γδ T cells are associated with immune responses to both liver-stage and blood-stage Plasmodium infection. The immune responses of T cell-lineages to Plasmodium infection are associated with both protection and immunopathology. Studies with mouse model of malaria contribute to our understanding of host immune response. In this paper, we focus primarily on mouse malaria model with blood-stage Plasmodium berghei infection and review our knowledge of T cell immune responses against Plasmodium infection. Moreover, we also discuss findings of experimental human studies. Uncovering the precise mechanisms of T cell-mediated immunity to Plasmodium infection can be accomplished through further investigations using mouse models of malaria with rodent Plasmodium parasites. Those findings would be invaluable to advance the efforts for development of an effective malaria vaccine. [ABSTRACT FROM AUTHOR]

Background: Chemical allergies are T cell-mediated diseases that often manifest in the skin as allergic contact dermatitis (ACD). To prevent ACD on a public health scale and avoid elicitation reactions at the individual patient level, predictive and diagnostic tests, respectively, are indispensable. Currently, there is no validated in vitro T cell assay available. The main bottlenecks concern the inefficient generation of T cell epitopes and the detection of rare antigen-specific T cells. Methods: Here, we systematically review original experimental research papers describing T cell activation to chemical skin sensitizers. We focus our search on studies published in the PubMed and Scopus databases on non-metallic allergens in the last 20 years. Results: We identified 37 papers, among them 32 (86%) describing antigen-specific human T cell activation to 31 different chemical allergens. The remaining studies measured the general effects of chemical allergens on T cell function (five studies, 14%). Most antigen-specific studies used peripheral blood mononuclear cells (PBMC) as antigen-presenting cells (APC, 75%) and interrogated the blood T cell pool (91%). Depending on the individual chemical properties, T cell epitopes were generated either by direct administration into the culture medium (72%), separate modification of autologous APC (29%) or by use of hapten-modified model proteins (13%). Read-outs were mainly based on proliferation (91%), often combined with cytokine secretion (53%). The analysis of T cell clones offers additional opportunities to elucidate the mechanisms of epitope formation and cross-reactivity (13%). The best researched allergen was p-phenylenediamine (PPD, 12 studies, 38%). For this and some other allergens, stronger immune responses were observed in some allergic patients (15/31 chemicals, 48%), illustrating the in vivo relevance of the identified T cells while detection limits remain challenging in many cases. Interpretation: Our results illustrate current hardships and possible solutions to monitoring T cell responses to individual chemical skin sensitizers. The provided data can guide the further development of T cell assays to unfold their full predictive and diagnostic potential, including cross-reactivity assessments. [ABSTRACT FROM AUTHOR]

Simple Summary: The following paper was developed as a reference for healthcare workers who are looking for information on advanced non-small cell lung cancers that lack driver mutations and their treatment with immunotherapy. The aim of the present study is to provide a reliable data source based on a review of the most current papers on the PD-1/PD-L1 and CTLA-4 inhibitors, as well as their use in medical practice. From a complete literature review, we were able to present in this paper what is most current in the treatment with immunotherapy for advanced non-small cell lung cancer (NSCLC). Especially the use of immunotherapy, particularly inhibitors of PD-1 (programmed cell death protein 1), PDL-1 (programmed cell death protein ligand 1), and CTLA-4 (cytotoxic T-lymphocyte antigen 4). Since 2015, these drugs have transformed the treatment of advanced NSCLC lacking driver mutations, evolving from second-line therapy to first-line, with excellent results. The arrival of new checkpoint inhibitors such as cemiplimab and the use of checkpoint inhibitors earlier in the therapy of advanced and metastatic cancers has been making the future prospects for treating NSCLC lacking driver mutations more favorable and optimistic. In addition, for those patients who have low PDL-1 positivity tumors, the combination of cytotoxic chemotherapy, VEGF inhibitor, and immunotherapy have shown an important improvement in global survival and progression free survival regardless the PDL-1 status. We also explored the effectiveness of adding radiotherapy to immunotherapy and the most current results about this combination. One concern that cannot be overlooked is the safety profile of immune checkpoint inhibitors (ICI) and the most common toxicities are described throughout this paper as well as tumor resistance to ICI. [ABSTRACT FROM AUTHOR]

Various categories of coronavirus disease 19 (COVID-19) patients have exhibited major mortality rate differences and symptoms. Some papers have recently explained these differences in mortality rates and symptoms as a consequence of this virus infection acting in synergy with one or more latent pathogen infections in some patients. A latent pathogen infection likely to be involved in millions of these patients is the protozoan parasite Toxoplasma gondii , which infects approximately one third of the global human population. However, other papers have concluded that latent protozoan parasite infections can reduce the severity of viral infections. The aims and purposes of this paper include providing explanations for the contradictions between these studies and introducing a significant new category of T-cell exhaustion. Latent pathogens can have different genetic strains with great differences in their effects on a second pathogen infection. Furthermore, depending on the timing and effectiveness of drug treatments, pathogen infections that become latent may or may not later induce immune cell dysfunctions, including T-cell exhaustion. Concurrent multiple pathogen T-cell exhaustion is herein called "polyspecific T-cell exhaustion." • COVID-19 patients exhibit mortality rate differences probably from latent pathogen infections. • Toxoplasma gondii infects about one third of the global human population and it is likely involved. • Latent pathogens have different genetic strains & different effects on later pathogen infections. • Drug treatments affect pathogen infections causing immune dysfunctions, e.g. T-cell exhaustion. • "Polyspecific T-cell exhaustion" enables concurrent multiple pathogen T-cell exhaustion. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer has remained the leading cause of death among gynecologic malignancies. The current standard of treatment, in most cases, is a combination of surgery and chemotherapy, based on platinum agents and taxanes. Despite the increasing usage of newer drug groups, such as bevacizumab and PARP inhibitors, and the expansion of patient groups for these drugs, ovarian cancer is characterized by recurrences, particularly in the form of peritoneal implants. This review focuses on immunotherapy for ovarian cancer. It considers the current state of knowledge in areas such as cancer vaccines, adoptive cell therapy, CAR-T therapy, and anti-CTLA-4 monotherapy. The paper specifically considers PD-1/PDL-1 as drug targets. Anti-PD-1/PD-L1 monotherapy, and anti-PD-1/PD-L1 immunotherapy in combination with other agents, are analyzed. Ovarian cancer is one of the most fatal cancers in women worldwide. Cytoreductive surgery combined with platinum-based chemotherapy has been the current first-line treatment standard. Nevertheless, ovarian cancer appears to have a high recurrence rate and mortality. Immunological processes play a significant role in tumorigenesis. The production of ligands for checkpoint receptors can be a very effective, and undesirable, immunosuppressive mechanism for cancers. The CTLA-4 protein, as well as the PD-1 receptor and its PD-L1 ligand, are among the better-known components of the control points. The aim of this paper was to review current research on immunotherapy in the treatment of ovarian cancer. The authors specifically considered immune checkpoints molecules such as PD-1/PDL-1 as targets for immunotherapy. We found that immune checkpoint-inhibitor therapy does not have an improved prognosis in ovarian cancer; although early trials showed that a combination of anti-PD-1/PD-L1 therapy with targeted therapy might have the potential to improve responses and outcomes in selected patients. However, we must wait for the final results of the trials. It seems important to identify a group of patients who could benefit significantly from treatment with immune checkpoints inhibitors. However, despite numerous trials, ICIs have not become part of routine clinical practice for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

• This paper compares and analyzes the difference of immune status of T lymphocytes and their subsets in hepatitis B patients under different ALT conditions for the first time. • For the first time, this paper reveals the changes of immune status and the effects of antiviral therapy on immune function when ALT is greater than or equal to 2 times the normal upper limit. • This paper puts forward for the first time the significance of using ALT as a node to judge the immune function of the body. The aim of the present study was to explore the effect of hepatitis B virus on T lymphocyte and its subsets in different ALT states, and elucidate the immunological mechanism of ALT basing antiviral therapy for hepatitis B. 363 chronic hepatitis B patients were selected as the study subjects. According to ALT abnormalities, the patients were divided into three study groups. ALT normal group 131 cases, normal≦ ALT < 2 times of upper limit group 110 cases, ALT ≥ 2 times of upper limit group 122 cases. Entecavir was given to the ALT ≥ 2 times of upper limit group patients and followed up for 24 weeks. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the hepatitis B virus load were measured by quantitative PCR analyzer, T lymphocytes were detected by flow cytometry, the level of IL-2, IFN-γ, IL-4 and IL-10 were detected by enzyme-linked immunosorbent assay. Detecting the influence of different hepatitis B viru loads in different groups on immunological indexes, and the virological and immunological indexes changes in before and after antiviral therapy patients. In the ALT normal group, different virus load hepatitis B virus had minor effect on T lymphocytes and their subsets (P > 0.05). In the ALT ≥ double upper limit of normal group. with the virus load increased, The total number of T lymphocytes, CD3+ CD4 + T lymphocytes decreased, (P < 0.05)CD3+ CD8 + T lymphocytes increased(P < 0.05). With the virus load increased the cytokines IL-2, IFN-γ which reflect the Th1 lymphocytes increased(P < 0.05), the cytokines IL-4、IL-10 which reflect the Th2 lymphocytes decreased(P < 0.05). Before and after 24 weeks of entecavir treatment, the patient's HBV-DNA decreased significantly(P < 0.05) and the body's immune function improved significantly. (P < 0.05)The influence of hepatitis B virus on immune function is different in different ALT states. Therefore, the scientific significance of ALT grouping in the hepatitis B treatment can be clarified from the immunological point. [ABSTRACT FROM AUTHOR]

• We systematically and in detail summarize the classification and biological characteristics of DC, as well as its development process. We focus on and deeply understand the role of DC in regulating the pathogenesis of different allergic diseases. • We demonstrate for the frist time the role of dendritic cells in various allergic diseases including AR, AA, AD, and FA. • Based on inflammatory response and immune regulation, a better understanding of the role of DC in immunomodulation and Th2 immune response can guide the development of new therapeutic targets for various allergic diseases and provide new ideas for the treatment of patients with allergic diseases. Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases. [ABSTRACT FROM AUTHOR]

Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research. [Display omitted] [ABSTRACT FROM AUTHOR]

The newly discovered subset of memory T cells, tissue resident memory T (TRM) cells, reside in peripheral tissues for a long time, contributing to a rapid immune response and constituting the first line of defense when pathogens invade cells. Tissue resident memory T cells have unique transcriptome characteristics, and their presence in peripheral tissues is regulated by many factors. TRM cells residing in different tissues often express different surface markers. In addition to CD8+ and CD4+ T cells, which are the best-characterized T cells, Treg cells and various innate T cells can reside in nonlymphoid tissues. Many recent studies have shown that tissue resident memory T cells play indispensable roles in tumor immunity and allergic diseases. This paper reviews the differentiation, regulation, variety and function of TRM cells and the roles they play in skin diseases, including cutaneous melanoma and psoriasis. • Tissue-resident memory T cells exhibit distinct tissue-specific and niche-specific functions in immune detection network. • Multiple factors control the development and resident of Tissue-resident memory T cell. • Tissue-resident memory T cells participate in skin inflammation and contribute tomaintaining the recurrence of skin diseases. [ABSTRACT FROM AUTHOR]

This paper presents a high-stability low-power 10 T (HSLP10T) sub-threshold SRAM cell with single-ended operations. The HSLP10T cell uses a decoupled read path, formed by a transmission gate and a dynamic inverter, thereby, resulting in read stability improvement. In addition, it employs a feedback-cutting transistor to facilitate the write operation, which increases writability. Due to single-ended operations, direct-write on complementary node, floated bitline, and use of more p-type transistors, the power consumption reduces in the proposed cell. Simulated results in the 7-nm FinFET technology indicate that at a 300 mV supply voltage, the read stability/writability of the proposed HSLP10T cell is 2.06X/1.31X as that of the conventional 6 T cell. Moreover, the dynamic/leakage power consumption is reduced by 1.82X/2.92X when compared with the conventional 6 T SRAM. The proposed HSLP10T SRAM bitcell has a layout area of 0.047 µm2, which is 1.67 × larger than the conventional 6 T SRAM. However, the highest ON-to-OFF currents ratio related to the proposed design compensates for this area overhead by connecting more number of cells to the same bitline in the columns of the SRAM array. Moreover, the minimum operation voltage is reduced by 48.28 % using proposed design compared to the conventional 6 T SRAM. [ABSTRACT FROM AUTHOR]

Psoriasis is a common inflammatory skin disease involving interactions between keratinocytes and immune cells that significantly affects the quality of life. It is characterized by hyperproliferation and abnormal differentiation of keratinocytes and excessive infiltration of immune cells in the dermis and epidermis. The immune mechanism underlying this disease has been elucidated in the past few years. Research shows that psoriasis is regulated by the complex interactions among immune cells, such as keratinocytes, dendritic cells, T lymphocytes, neutrophils, macrophages, natural killer cells, mast cells, and other immune cells. An increasing number of signaling pathways have been found to be involved in the pathogenesis of psoriasis, which has prompted the search for new treatment targets. In the past decades, studies on the pathogenesis of psoriasis have focused on the development of targeted and highly effective therapies. In this review, we have discussed the relationship between various types of immune cells and psoriasis and summarized the major signaling pathways involved in the pathogenesis of psoriasis, including the PI3K/AKT/mTOR, JAK-STAT, JNK, and WNT pathways. In addition, we have discussed the results of the latest omics research on psoriasis and the epigenetics of the disease, which provide insights regarding its pathogenesis and therapeutic prospects; we have also summarized its treatment strategies and observations of clinical trials. In this paper, the various aspects of psoriasis are described in detail, and the limitations of the current treatment methods are emphasized. It is necessary to improve and innovate treatment methods from the molecular level of pathogenesis, and further provide new ideas for the treatment and research of psoriasis. • The relationship between various immune cells and psoriasis is discussed. • Major signaling pathways involved in the pathogenesis of psoriasis are summarized. • Results of the latest omics research on psoriasis are discussed. • Treatment strategies and clinical trial observations for psoriasis are summarized. [ABSTRACT FROM AUTHOR]

• We systematically and in detail summarize the classification and biological characteristics of DC, as well as its development process. We focus on and deeply understand the role of DC in regulating the pathogenesis of different allergic diseases. • We demonstrate for the frist time the role of dendritic cells in various allergic diseases including AR, AA, AD, and FA. • Based on inflammatory response and immune regulation, a better understanding of the role of DC in immunomodulation and Th2 immune response can guide the development of new therapeutic targets for various allergic diseases and provide new ideas for the treatment of patients with allergic diseases. Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases. [ABSTRACT FROM AUTHOR]

As genetically engineered cells, chimeric antigen receptor (CAR)-T cells express specific receptors on their surface to target and eliminate malignant cells. CAR proteins are equipped with elements that enhance the activity and survival of T cells. Once injected, CAR-T cells act as a "living drug" against tumor cells in the body. Up to now, CAR-T cell therapy has been demonstrated as a robust adoptive cell transfer (ACT) immunotherapeutic modality for eliminating tumor cells in refractory hematological malignancies. CAR-T cell therapy modality involves several steps, including the collecting of the blood from patients, the isolation of peripheral blood mononuclear cells (PBMCs), the enrichment of CD4+/CD8+ T cell, the genetic reprogramming, the expansion of modified T cells, and the injection of genetically engineered T cells. The production of CAR-T cells is a multi-step procedure, which needs precise and safety management systems, including good manufacturing practice (GMP), and in-line quality control and assurance. The current study describes the structure of CARs and concentrates on the next generations of CARs that are engaged in enhancing the anti-tumor responses and safety of the engineered T cells. This paper also highlights the important concerns in quality control and nonclinical research of CAR-T cells, as well as general insights into the manufacture, reprogramming, and application of CAR-T cells based on new and enhanced techniques for treating hematological malignancies. Besides, the application of the CRISPR-Cas9 genome editing technology and nanocarrier-based delivery systems containing CAR coding sequences to overcome the limitations of CAR-T cell therapy has also been explained. [Display omitted] [ABSTRACT FROM AUTHOR]

First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Chiara Cassioli is first author on 'The Bardet-Biedl syndrome complex component BBS1 controls T cell polarity during immune synapse assembly', published in JCS. Chiara is a postdoc in the lab of Cosima T. Baldari at the University of Siena, Italy, investigating regulation of immune synapse assembly in the non-ciliated T cells by components of the ciliary machinery. [ABSTRACT FROM AUTHOR]