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

Research output: Contribution to journalReview article

56 Citations (Scopus)

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.

Original languageEnglish (US)
Article number40
JournalJournal for ImmunoTherapy of Cancer
Volume4
Issue number1
DOIs
StatePublished - Jul 19 2016

Fingerprint

Carcinogenesis
B-Lymphocytes
Regulatory B-Lymphocytes
Neoplasms
Natural Killer Cells
T-Lymphocytes
Interleukin-10
Ligands
B-Lymphocyte Subsets
Tumor Microenvironment
Adaptive Immunity
Collagenases
Regulatory T-Lymphocytes
Immunosuppressive Agents
Cellular Immunity
Non-Small Cell Lung Carcinoma
Anti-Idiotypic Antibodies
Hepatocellular Carcinoma
Immunity
Stomach

Keywords

  • Anti-tumor immunity
  • B regulatory cells
  • Carcinogenesis

ASJC Scopus subject areas

  • Oncology
  • Immunology and Allergy
  • Cancer Research
  • Molecular Medicine
  • Pharmacology
  • Immunology

Cite this

B cell regulation of the anti-tumor response and role in carcinogenesis. / Schwartz, Marc; Zhang, Yu; Rosenblatt, Joseph D.

In: Journal for ImmunoTherapy of Cancer, Vol. 4, No. 1, 40, 19.07.2016.

Research output: Contribution to journalReview article

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