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B cell regulation of the anti-tumor response and role in carcinogenesis
- Source :
- Journal for Immunotherapy of Cancer
- Publication Year :
- 2016
- Publisher :
- BMJ, 2016.
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
Carcinogenesis
T cell
Immunology
Review
Biology
Natural killer cell
03 medical and health sciences
0302 clinical medicine
medicine
Immunology and Allergy
Antigen-presenting cell
Pharmacology
Lymphokine-activated killer cell
B regulatory cells
Natural killer T cell
Acquired immune system
3. Good health
Cell biology
B-1 cell
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Myeloid-derived Suppressor Cell
Anti-tumor immunity
Molecular Medicine
Subjects
Details
- ISSN :
- 20511426
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal for ImmunoTherapy of Cancer
- Accession number :
- edsair.doi.dedup.....839544806a3651e2b09746229f12808f