title: B cell regulation of the anti-tumor response and role in carcinogenesis.
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.
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, 1120 NW 14th St., CRB 610, Miami, FL 33136 USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Schwartz
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, 1120 NW 14th St., CRB 610, Miami, FL 33136 USA ; Department of Medicine, University of Miami Miller School of Medicine, 1120 NW 14th St., CRB 610, Miami, FL 33136 USA ; UM Sylvester Comprehensive Cancer Center, 1120 NW 14th St., CRB 610, Miami, FL 33136 USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, 1120 NW 14th St., CRB 610, Miami, FL 33136 USA ; Department of Medicine, University of Miami Miller School of Medicine, 1120 NW 14th St., CRB 610, Miami, FL 33136 USA ; UM Sylvester Comprehensive Cancer Center, 1120 NW 14th St., CRB 610, Miami, FL 33136 USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Rosenblatt
keywords: Anti-tumor immunity; B regulatory cells; Carcinogenesis