Fig. 1

Tumor educated B regulatory cells suppress anti-tumor immunity. Tumor cell secreted chemokines such as CXCL13, may attract naïve B cells into the tumor microenvironment. Tumor cells and tumor infiltrating Treg cells may express inhibitory molecules (e.g. PD-L1) and/or secrete cytokines (e.g. IL-21, IL-35, or TGF-β) that may promote differentiation of B cells leading to development of a B regulatory phenotype (Breg cells). Breg cells may undergo activation of Stat3, and also upregulate key regulatory or inhibitory molecules such as PD-L1, CD25, CD86, LAP/TGF-β, and Granzyme B, and secrete cytokines, such as IL-10, IL-35 and TGF-β. Breg cells can suppress T and NK cell activation, proliferation and function in vivo and also ‘educate’ MDSC and tumor associated macrophages (TAM) to suppress anti-tumor immunity. Breg cells have also been noted to support natural Treg cell expansion and the conversion of effector CD4+ T cells into inducible Treg cells. Breg cells may also facilitate macrophage differentiation into TAM-M2 macrophages and increase local inflammation and thereby promote carcinogenesis in certain settings. Further details and supporting references in text