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B cell regulation of the anti-tumor response and role in carcinogenesis

Authors
  • Schwartz, Marc1
  • Zhang, Yu2, 1, 3
  • Rosenblatt, Joseph D.2, 1, 3
  • 1 University of Miami Miller School of Medicine, Department of Medicine, 1120 NW 14th St., CRB 610, Miami, FL, 33136, USA , Miami (United States)
  • 2 University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, 1120 NW 14th St., CRB 610, Miami, FL, 33136, USA , Miami (United States)
  • 3 UM Sylvester Comprehensive Cancer Center, 1120 NW 14th St., CRB 610, Miami, FL, 33136, USA , Miami (United States)
Type
Published Article
Journal
Journal for ImmunoTherapy of Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jul 19, 2016
Volume
4
Issue
1
Identifiers
DOI: 10.1186/s40425-016-0145-x
Source
Springer Nature
Keywords
License
Green

Abstract

The balance between immune effector cells such as T cells and natural killer cells, and immunosuppressive Treg cells, dendritic, myeloid and monocytic sub-populations in the tumor microenvironment acts to calibrate the immune response to malignant cells. Accumulating evidence is pointing to a role for B cells in modulating the immune response to both solid tumors and hematologic cancer. Evidence from murine autoimmune models has defined B regulatory cell (Breg) subsets that express cytokines such as IL-10, TGF-β, and/or express immune regulatory ligands such as PD-L1, which can suppress T cell and/or natural killer cell responses. Multiple murine tumor models exhibit decreased tumor growth in B cell deficient or B cell depleted mice. In several of these models, B cells inhibit T cell mediated tumor immunity and/or facilitate conversion of T cells to CD4+CD25+FoxP3+ T regs, which act to attenuate the innate and/or adaptive antitumor immune response. Mechanisms of suppression include the acquisition of inhibitory ligand expression, and phosphorylation of Stat3, and induction of IL-10 and TGF-β, resulting in a Breg phenotype. Breg suppressive activity may affect diverse cell subtypes, including T effector cells, NK cells, myeloid derived suppressor cells (MDSC) and/or tumor associated macrophages. B cells may also directly promote tumorigenesis through recruitment of inflammatory cells, and upregulation of pro-angiogenic genes and pro-metastatic collagenases. Breg infiltration has now been identified in a variety of solid tumor malignancies including but not limited to ovarian, gastric, non-small cell lung cancer, pancreatic, esophageal, head and neck, and hepatocellular carcinomas. Increasing evidence suggests that recruitment of B cells and acquisition of suppressive activity within the tumor bed may be an important mechanism through which B cells may modulate innate and/or adaptive anti-tumor immunity. B cell depletion in the clinic using anti-CD20 antibodies and/or inhibitors of BTK and/or other signaling pathways, may be a useful strategy for augmenting the anti-tumor immune response.

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