Duality of B Cell-CXCL13 Axis in Tumor Immunology

Abstract

Tumor immunity is a rapidly evolving area of research consisting of many possible permutations of immune cell tumor interactions that are dependent upon cell type, tumor type, and stage in tumor progression. At the same time, the majority of cancer immunotherapies have been focused on modulating the T cell-mediated antitumor immune response and have largely ignored the potential utility that B cells possess with respect to tumor immunity. Therefore, this motivated an exploration into the role that B cells and their accompanying chemokine, CXCL13, play in tumor immunity across multiple tumor types. Both B cells and CXCL13 possess dualistic impacts on tumor progression and tumor immunity which is furthered detail in this review. Specifically, various B cells subtypes are able to suppress or enhance several important immunological functions. Paradoxically, CXCL13 has been shown to drive several pro-growth and invasive signaling pathways across multiple tumor types, while also, correlating with improved survival and immune cell tumor localization in other tumor types. Potential tools for better elucidating the mechanisms by which B cells and CXCL13 impact the antitumor immune response are also discussed. In addition, multiples strategies are proposed for modulating the B cell-CXCL13 axis for cancer immunotherapies.

Role of the tumor immune microenvironment in tumor immunotherapy (Review)

“…Antibody-induced circulating immune complexes can inhibit antitumor immune response, leading to poor prognosis in patients with pancreatic ductal adenocarcinoma and bone marrow tumors ( 24 , 25 ). Lymphotoxin secreted by B cells can accelerate tumor angiogenesis via activating STAT3 signaling, which in turn promotes cell proliferation in prostate cancer, melanoma and lung cancer ( 26 ). B cells can also promote bladder cancer metastasis by increasing the expression of extracellular matrix and remodeling-related genes ( 27 ).…”

“…B cells can also promote bladder cancer metastasis by increasing the expression of extracellular matrix and remodeling-related genes ( 27 ). B cells, by secreting TGF-β, promote the production of reactive oxygen species and nitric oxide in myeloid cells, as well as the transformation of CD4 + T cells into Tregs, thereby suppressing the function of CD4 + T, CD8 + T and NK cells, and accelerating tumor growth and metastasis ( 26 , 28 ). CD20 monoclonal antibody was found to restrain the function of CD4 + and CD8 + T cells in melanoma ( 26 ).…”

Current Perspectives on B Lymphocytes in the Immunobiology of Hepatocellular Carcinoma

“…IL-10 can inhibit other stimulating cytokines’ production, causing a decrease in the reactivity of NK cells, Th1 cells, and CD8 + T cells. The TGF-β production can drive the conversion of CD4 + T cells into Tregs, thereby inhibiting Natural Killer (NK) cells and CD8 + T cells, which are critical to inhibit the growth of tumors ( 47 – 49 ). Lindner et al.…”

Integrative Analysis of Gene Expression Based on Multi-Omics Databases Identified CXC Chemokines as Immune Prognostic Biomarkers of Rectal Adenocarcinoma

“…In terms of mechanism, downregulated CXCL13 may reduce B cells and Tfh cells in ltration, and thus lead to READ progression and poor prognosis, which is similar to breast cancer [57] and colorectal cancer [58]. These ndings indicate the dual character of CXCL13, similar to CXCL3, in different tumors [59], and CXCL13 mainly performs anti-tumor effect on READ.…”