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Nature Reviews. Cancer Jul 2022Although immunotherapy research to date has focused largely on T cells, there is mounting evidence that tumour-infiltrating B cells and plasma cells (collectively... (Review)
Review
Although immunotherapy research to date has focused largely on T cells, there is mounting evidence that tumour-infiltrating B cells and plasma cells (collectively referred to as tumour-infiltrating B lymphocytes (TIL-Bs)) have a crucial, synergistic role in tumour control. In many cancers, TIL-Bs have demonstrated strong predictive and prognostic significance in the context of both standard treatments and immune checkpoint blockade, offering the prospect of new therapeutic opportunities that leverage their unique immunological properties. Drawing insights from autoimmunity, we review the molecular phenotypes, architectural contexts, antigen specificities, effector mechanisms and regulatory pathways relevant to TIL-Bs in human cancer. Although the field is young, the emerging picture is that TIL-Bs promote antitumour immunity through their unique mode of antigen presentation to T cells; their role in assembling and perpetuating immunologically 'hot' tumour microenvironments involving T cells, myeloid cells and natural killer cells; and their potential to combat immune editing and tumour heterogeneity through the easing of self-tolerance mechanisms. We end by discussing the most promising approaches to enhance TIL-B responses in concert with other immune cell subsets to extend the reach, potency and durability of cancer immunotherapy.
Topics: B-Lymphocytes; Humans; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Neoplasms; Tumor Microenvironment
PubMed: 35393541
DOI: 10.1038/s41568-022-00466-1 -
Frontiers in Immunology 2021Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting... (Review)
Review
Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.
Topics: Animals; B-Lymphocyte Subsets; B-Lymphocytes, Regulatory; Biomarkers; Cell Differentiation; Cytokines; Gene Expression Regulation; Humans; Immunomodulation; T-Lymphocyte Subsets
PubMed: 33995344
DOI: 10.3389/fimmu.2021.611795 -
Annual Review of Cell and Developmental... Oct 2020Innate and adaptive immune responses decline with age, leading to greater susceptibility to infectious diseases and reduced responses to vaccines. Diseases are more... (Review)
Review
Innate and adaptive immune responses decline with age, leading to greater susceptibility to infectious diseases and reduced responses to vaccines. Diseases are more severe in old than in young individuals and have a greater impact on health outcomes such as morbidity, disability, and mortality. Aging is characterized by increased low-grade chronic inflammation, so-called inflammaging, that represents a link between changes in immune cells and a number of diseases and syndromes typical of old age. In this review we summarize current knowledge on age-associated changes in immune cells with special emphasis on B cells, which are more inflammatory and less responsive to infections and vaccines in the elderly. We highlight recent findings on factors and pathways contributing to inflammaging and how these lead to dysfunctional immune responses. We summarize recent published studies showing that adipose tissue, which increases in size with aging, contributes to inflammaging and dysregulated B cell function.
Topics: Animals; Antibody Formation; B-Lymphocytes; Gastrointestinal Microbiome; Humans; Immunosenescence; Inflammation; Polymorphism, Single Nucleotide
PubMed: 33021823
DOI: 10.1146/annurev-cellbio-011620-034148 -
Rheumatology (Oxford, England) Dec 2021SS is a chronic, autoimmune condition characterized by lymphocytic infiltration of the exocrine glands and B-cell dysfunction. Current treatment strategies are largely... (Review)
Review
SS is a chronic, autoimmune condition characterized by lymphocytic infiltration of the exocrine glands and B-cell dysfunction. Current treatment strategies are largely empirical and offer only symptomatic relief for patients. There are no proven treatments that alter disease progression or treat the systemic manifestations of disease. B-cell depletion is used in patients with systemic disease but its overall clinical efficacy has not been demonstrated in two large randomized controlled trials. Studies are now focussing on alternative strategies to target B-cells, including co-stimulation targets, with promising data. It is increasingly clear that clinical trials in SS will require patient stratification and relevant and sensitive outcome measures to identify successful treatment modalities.
Topics: B-Lymphocytes; Biological Therapy; Humans; Sjogren's Syndrome
PubMed: 34951923
DOI: 10.1093/rheumatology/keab466 -
Nature Immunology Jan 2022Memory B cells (MBCs) protect the body from recurring infections. MBCs differ from their naive counterparts (NBCs) in many ways, but functional and surface marker...
Memory B cells (MBCs) protect the body from recurring infections. MBCs differ from their naive counterparts (NBCs) in many ways, but functional and surface marker differences are poorly characterized. In addition, although mice are the prevalent model for human immunology, information is limited concerning the nature of homology in B cell compartments. To address this, we undertook an unbiased, large-scale screening of both human and mouse MBCs for their differential expression of surface markers. By correlating the expression of such markers with extensive panels of known markers in high-dimensional flow cytometry, we comprehensively identified numerous surface proteins that are differentially expressed between MBCs and NBCs. The combination of these markers allows for the identification of MBCs in humans and mice and provides insight into their functional differences. These results will greatly enhance understanding of humoral immunity and can be used to improve immune monitoring.
Topics: Animals; B-Lymphocytes; Biomarkers; Female; Flow Cytometry; Humans; Immunity, Humoral; Immunologic Memory; Male; Memory B Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Phenotype
PubMed: 34937918
DOI: 10.1038/s41590-021-01078-x -
Frontiers in Immunology 2021B cells are central to the pathogenesis of multiple autoimmune diseases, through antigen presentation, cytokine secretion, and the production of autoantibodies. During... (Review)
Review
B cells are central to the pathogenesis of multiple autoimmune diseases, through antigen presentation, cytokine secretion, and the production of autoantibodies. During development and differentiation, B cells undergo drastic changes in their physiology. It is emerging that these are accompanied by equally significant shifts in metabolic phenotype, which may themselves also drive and enforce the functional properties of the cell. The dysfunction of B cells during autoimmunity is characterised by the breaching of tolerogenic checkpoints, and there is developing evidence that the metabolic state of B cells may contribute to this. Determining the metabolic phenotype of B cells in autoimmunity is an area of active study, and is important because intervention by metabolism-altering therapeutic approaches may represent an attractive treatment target.
Topics: Autoimmune Diseases; Autoimmunity; Autophagy; B-Lymphocytes; Biomarkers; Disease Susceptibility; Energy Metabolism; Humans; Lymphocyte Activation; Lymphopoiesis; Molecular Targeted Therapy
PubMed: 34163480
DOI: 10.3389/fimmu.2021.681105 -
Cancer Cell Oct 2021Tumor-infiltrating B cells complement T cell-mediated antitumor immunity. A panel of experts share their views on the complexity of B cells within the tumor... (Review)
Review
Tumor-infiltrating B cells complement T cell-mediated antitumor immunity. A panel of experts share their views on the complexity of B cells within the tumor microenvironment, the variety of mechanisms by which these cells control tumor growth, their organization in tertiary lymphoid structures, and their association with immunotherapy response.
Topics: B-Lymphocytes; Humans; Lymphocytes, Tumor-Infiltrating; Neoplasms
PubMed: 34597591
DOI: 10.1016/j.ccell.2021.09.007 -
Current Opinion in Immunology Dec 2019FDA-approved B cell-targeted therapy has expanded to a multitude of autoimmune diseases ranging from organ specific diseases, like pemphigus and multiple sclerosis, to... (Review)
Review
PURPOSE OF REVIEW
FDA-approved B cell-targeted therapy has expanded to a multitude of autoimmune diseases ranging from organ specific diseases, like pemphigus and multiple sclerosis, to systemic diseases such as ANCA-associated vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this review, we discuss the variability in response to B cell-targeted therapies with a focus on the diversity of human B cells and plasma cells, and will discuss several of the promising new B cell-targeted therapies.
RECENT FINDING
The pathogenic roles for B cells include autoantibody-dependent and autoantibody-independent functions whose importance may vary across diseases or even in subsets of patients with the same disease. Recent data have further demonstrated the diversity of human B cell subsets that contribute to disease as well as novel pathways of B cell activation in autoimmune disease. The importance of eliminating autoreactive B cells and plasma cells will be discussed, as well as new approaches to do so.
SUMMARY
The past several years has witnessed significant advances in our knowledge of human B cell subsets and function. This has created a nuanced picture of the diverse ways B cells contribute to autoimmunity and an ever-expanding armamentarium of B cell-targeted therapies.
Topics: Animals; Antibodies, Monoclonal; Autoantibodies; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Biomarkers; Disease Management; Disease Susceptibility; Humans; Lymphocyte Depletion; Molecular Targeted Therapy; T-Lymphocytes; Treatment Outcome
PubMed: 31733607
DOI: 10.1016/j.coi.2019.09.004 -
Immunity Dec 2020Activated B cells participate in either extrafollicular (EF) or germinal center (GC) responses. Canonical responses are composed of a short wave of plasmablasts (PBs)... (Review)
Review
Activated B cells participate in either extrafollicular (EF) or germinal center (GC) responses. Canonical responses are composed of a short wave of plasmablasts (PBs) arising from EF sites, followed by GC producing somatically mutated memory B cells (MBC) and long-lived plasma cells. However, somatic hypermutation (SHM) and affinity maturation can take place at both sites, and a substantial fraction of MBC are produced prior to GC formation. Infection responses range from GC responses that persist for months to persistent EF responses with dominant suppression of GCs. Here, we review the current understanding of the functional output of EF and GC responses and the molecular switches promoting them. We discuss the signals that regulate the magnitude and duration of these responses, and outline gaps in knowledge and important areas of inquiry. Understanding such molecular switches will be critical for vaccine development, interpretation of vaccine efficacy and the treatment for autoimmune diseases.
Topics: Animals; Autoimmune Diseases; B-Lymphocyte Subsets; B-Lymphocytes; Germinal Center; Humans; Immunity; Immunoglobulin Class Switching; Infections; Lymphocyte Activation; Plasma Cells; Vaccines
PubMed: 33326765
DOI: 10.1016/j.immuni.2020.11.006 -
Journal of Hematology & Oncology Sep 2020B cell maturation antigen (BCMA) is a novel treatment target for multiple myeloma (MM) due to its highly selective expression in malignant plasma cells (PCs). Multiple... (Review)
Review
B cell maturation antigen (BCMA) is a novel treatment target for multiple myeloma (MM) due to its highly selective expression in malignant plasma cells (PCs). Multiple BCMA-targeted therapeutics, including antibody-drug conjugates (ADC), chimeric antigen receptor (CAR)-T cells, and bispecific T cell engagers (BiTE), have achieved remarkable clinical response in patients with relapsed and refractory MM. Belantamab mafodotin-blmf (GSK2857916), a BCMA-targeted ADC, has just been approved for highly refractory MM. In this article, we summarized the molecular and physiological properties of BCMA as well as BCMA-targeted immunotherapeutic agents in different stages of clinical development.
Topics: Antibodies, Bispecific; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; B-Cell Maturation Antigen; B-Lymphocytes; Clinical Trials as Topic; Humans; Immunoconjugates; Immunotherapy; Immunotherapy, Adoptive; Molecular Targeted Therapy; Multicenter Studies as Topic; Multiple Myeloma; Neoplasm Proteins; Plasma Cells; Protein Isoforms; Randomized Controlled Trials as Topic
PubMed: 32943087
DOI: 10.1186/s13045-020-00962-7