Search

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC. [ABSTRACT FROM AUTHOR]

Helminths are multicellular parasites that are a substantial problem for both human and veterinary medicine. According to estimates, 1.5 billion people suffer from their infection, resulting in decreased life quality and burdens for healthcare systems. On the other hand, these infections may alleviate autoimmune diseases and allergy symptoms. The immune system is programmed to combat infections; nevertheless, its effector mechanisms may result in immunopathologies and exacerbate clinical symptoms. This review summarizes the role of the immune response against worms, with an emphasis on the Th2 response, which is a hallmark of helminth infections. We characterize non-immune cells (enteric tuft cells—ETCs) responsible for detecting parasites, as well as the role of hematopoietic-derived cells (macrophages, basophils, eosinophils, neutrophils, innate lymphoid cells group 2—ILC2s, mast cells, T cells, and B cells) in initiating and sustaining the immune response, as well as the functions they play in granulomas. The aim of this paper is to review the existing knowledge regarding the immune response against helminths, to attempt to decipher the interactions between cells engaged in the response, and to indicate the gaps in the current knowledge. [ABSTRACT FROM AUTHOR]

Simple Summary: This article addresses the topic of primary immunodeficiencies, with particular emphasis on antibody deficiencies with near-normal immunoglobulin levels or hyperimmunoglobulinemia. This paper goes beyond genetics and emphasizes the importance of the immune system and particularly immune checkpoints and Epstein–Barr virus (EBV) reactivation in the context of these disorders. The article delves into the immune dysregulations occurring in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical picture of patients and, in the future, may contribute to the development of cancer, especially those related to hematological malignancies. Disturbances observed in the immunopathogenesis of the presented diseases go beyond the accepted scheme, with the development of PID largely associated only with genetic disorders, and the article emphasizes that the regulation of immunity and virus reactivation also contributes to the progression of PID. This study delves into the intricate landscape of primary immunodeficiencies, with a particular focus on antibody deficiencies characterized by near-normal immunoglobulin levels or hyperimmunoglobulinemia. Contrary to the conventional focus on genetic dysregulation, these studies investigate the key roles of immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, on selected subpopulations of T and B lymphocytes and their serum concentrations of soluble forms in patients recruited for the studies in healthy volunteers. In addition, the studies also show the role of Epstein–Barr virus (EBV) reactivation and interactions with tested pathways of immune checkpoints involved in the immunopathogenesis of this disease. By examining the context of antibody deficiencies, this study sheds light on the nuanced interplay of factors beyond genetics, particularly the immune dysregulations that occur in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical presentation of patients and may contribute to the development of cancer in the future, especially related to hematological malignancies. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS-IV) is one of the main active components extracted from the Chinese medicinal herb Astragali and serves as a marker for assessing the herb's quality. AS-IV is a tetracyclic triterpenoid saponin in the form of lanolin ester alcohol and exhibits various biological activities. This review article summarizes the chemical structure of AS-IV, its pharmacological effects, mechanism of action, applications, future prospects, potential weaknesses, and other unexplored biological activities, aiming at an overall analysis. Papers were retrieved from online electronic databases, such as PubMed, Web of Science, and CNKI, and data from studies conducted over the last 10 years on the pharmacological effects of AS—IV as well as its impact were collated. This review focuses on the pharmacological action of AS-IV, such as its anti-inflammatory effect, including suppressing inflammatory factors, increasing T and B lymphocyte proliferation, and inhibiting neutrophil adhesion-associated molecules; antioxidative stress, including scavenging reactive oxygen species, cellular scorching, and regulating mitochondrial gene mutations; neuroprotective effects, antifibrotic effects, and antitumor effects. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies. [ABSTRACT FROM AUTHOR]

An interesting inference drawn by some COVID-19 epidemiological models is that there exists a proportion of the population who are not susceptible to infection—even at the start of the current pandemic. This paper introduces a model of the immune response to a virus. This is based upon the same sort of mean-field dynamics as used in epidemiology. However, in place of the location, clinical status, and other attributes of people in an epidemiological model, we consider the state of a virus, B and T-lymphocytes, and the antibodies they generate. Our aim is to formalise some key hypotheses as to the mechanism of resistance. We present a series of simple simulations illustrating changes to the dynamics of the immune response under these hypotheses. These include attenuated viral cell entry, pre-existing cross-reactive humoral (antibody-mediated) immunity, and enhanced T-cell dependent immunity. Finally, we illustrate the potential application of this sort of model by illustrating variational inversion (using simulated data) of this model to illustrate its use in testing hypotheses. In principle, this furnishes a fast and efficient immunological assay—based on sequential serology—that provides a (1) quantitative measure of latent immunological responses and (2) a Bayes optimal classification of the different kinds of immunological response (c.f., glucose tolerance tests used to test for insulin resistance). This may be especially useful in assessing SARS-CoV-2 vaccines. [ABSTRACT FROM AUTHOR]

Diagnosing acute leukemia is the necessary prerequisite to treating it. Multi-classification on the gene expression data of acute leukemia is help for diagnosing it which contains B-cell acute lymphoblastic leukemia (BALL), T-cell acute lymphoblastic leukemia (TALL) and acute myeloid leukemia (AML). However, selecting cancer-causing genes is a challenging problem in performing multi-classification. In this paper, weighted gene co-expression networks are employed to divide the genes into groups. Based on the dividing groups, a new regularized multinomial regression with overlapping group lasso penalty (MROGL) has been presented to simultaneously perform multi-classification and select gene groups. By implementing this method on three-class acute leukemia data, the grouped genes which work synergistically are identified, and the overlapped genes shared by different groups are also highlighted. Moreover, MROGL outperforms other five methods on multi-classification accuracy. [ABSTRACT FROM AUTHOR]

The adoptive transfer of chimeric antigen receptor (CAR)-modified T cells is attracting growing interest for the treatment of malignant diseases. Early trials with anti-CD19 CAR T cells have achieved spectacular remissions in B-cell leukemia and lymphoma, so far refractory, very recently resulting in the Food and Drug Administration approval of CD19 CAR T cells for therapy. With further applications and increasing numbers of patients, the reproducible manufacture of high-quality clinical-grade CAR T cells is becoming an ever greater challenge. New processing techniques, quality-control mechanisms, and logistic developments are required to meet both medical needs and regulatory restrictions. This paper summarizes the state-of-the-art in manufacturing CAR T cells and the current challenges that need to be overcome to implement this type of cell therapy in the treatment of a variety of malignant diseases and in a greater number of patients. [ABSTRACT FROM AUTHOR]

Background: The B and T cells of the human adaptive immune system leverage a highly diverse repertoire of antigen-specific receptors to protect the human body from pathogens. The sequencing and analysis of immune repertoires is emerging as an important tool to understand immune responses, whether beneficial or harmful (in the case of autoimmunity). However, methods for studying these repertoires, and for directly comparing different immune repertoires, are lacking. Results: In this paper, we present a non-parametric method for directly comparing sequencing repertoires, with the goal of rigorously quantifying differences in V, D, and J gene segment utilization. This method, referred to as the Repertoire Dissimilarity Index (RDI), uses a bootstrapped subsampling approach to account for variance in sequencing depth, and, coupled with a data simulation approach, allows for direct quantification of the average variation between repertoires. We use the RDI method to recapitulate known differences in the formation of the CD4+ and CD8+ T cell repertoires, and further show that antigen-driven activation of naïve CD8+ T cells is more selective than in the CD4+ repertoire, resulting in a more specialized CD8+ memory repertoire. Conclusions: We prove that the RDI method is an accurate and versatile method for comparisons of immune repertoires. The RDI method has been implemented as an R package, and is available for download through Bitbucket. [ABSTRACT FROM AUTHOR]

Antigen processing and presentation and cytotoxic targeting depend on the activities of several lysosomal enzymes that require mannose 6-phosphate (M6P) sorting signals for efficient intracellular transport and localization. In this paper, we show that mice deficient in the formation of M6P residues exhibit significant loss of cathepsin proteases in B cells, leading to lysosomal dysfunction with accumulation of storage material, impaired antigen processing and presentation, and subsequent defects in B cell maturation and antibody production. The targeting of lysosomal and granular enzymes lacking M6P residues is less affected in dendritic cells and T cells and sufficient for maintenance of degradative and lytic functions. M6P deficiency also impairs serum immunoglobulin levels and antibody responses to vaccination in patients. Our data demonstrate the critical role of M6P-dependent transport routes for B cell functions in vivo and humoral immunity in mice and human. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia among adults. It is the clonal expansion of B cells expressing CD19 and CD5. Despite significant progress in treatment, CLL is still incurable. γδ T cells comprise an important subset of the cytotoxic T cells. Although γδ T cells in CLL are dysfunctional, they still can possibly be used for immunotherapy. The current paper reviews our understanding of γδ T lymphocytes in CLL. [ABSTRACT FROM AUTHOR]

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients' experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Ebadi et al papers. To view these articles, visit https://doi.org/10.1111/apt.15029 and https://doi.org/10.1111/apt.15091. [ABSTRACT FROM AUTHOR]

Tumor immunotherapy using gene-modified T cells has already met with considerable success in the treatment of metastatic melanoma and B cell lymphoma. With improving patient prognoses, new questions arise. In particular, the long-term consequences of treatment among individuals of childbearing age could now be considered. Former patients can carry a cohort of transgenic memory T cells long after treatment has ceased and the effector T cell population has contracted. When patients become parents well after treatment is completed, expectant mothers may still pass transgenic T cells to their unborn children. Consequences should be more measurable if the mother also breastfeeds the baby. Maternal T cells may shape immune responses in the child, can tolerize the child to maternal antigens, and might cause either beneficial or adverse effects in the offspring. The hypothesis put forth is that transgenic T cells transferred from mother to child during and after pregnancy might have consequences that have not been adequately considered to date. Depending on the targeted antigen and the MHC eventually required to present it, such transfer may be beneficial, uneventful or even damaging. Such potential consequences are addressed in this paper. The transgenic T cells might form a pocket of memory T cells in secondary lymphoid organs of the child, expand upon antigen stimulation, and react. However, simple measures might be devised to avoid any reason for concern. These considerations provide ample incentive to probe transgenerational transfer of transgenic T cells. [ABSTRACT FROM AUTHOR]

High titer of anti-β2-glycoprotein I antibodies (anti-β2GPI Ab) plays a pathogenic role in antiphospholipid syndrome (APS). Numerous studies have focused on the pathological mechanism in APS; however, little attention is paid to the immune mechanism of production of anti-β2GPI antibodies in APS. Our previous study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized with human β2-glycoprotein I (β2GPI). TLR4 is required for the activation of B cells and the production of autoantibody in mice treated with β2GPI. However, TLR4 provides a third signal for B cell activation and then promotes B cells better receiving signals from both B cell antigen receptor (BCR) and CD40, thus promoting B cell activation, surface molecules expression, anti-β2GPI Ab production, and cytokines secretion and making B cell functioning like an antigen presenting cell (APC). At the same time, TLR4 also promotes B cells producing antibodies by upregulating the expression of B-cell activating factor (BAFF). In this paper, we aim to review the functions of TLR4 in B cell immune response and antibody production in autoimmune disease APS and try to find a new way for the prevention and treatment of APS. [ABSTRACT FROM AUTHOR]