Regulatory B cells in anti-tumor immunity

Abstract

Advances in understanding of the immune microenvironment have highlighted the role of immunosuppressive T cell, myeloid, dendritic and monocytic sub-populations in inhibition of the anti-tumor immune response. The role of B cells in modulating the immune response to solid tumors as well as lymphoid malignancies is less well understood. Murine models of autoimmune disease have defined B regulatory cell (Breg) subsets with immune suppressive activity, including B cell subsets that express IL-10, and transforming growth factor-β, which can facilitate T regulatory cell recruitment and expansion. Multiple murine tumor models point to the existence of similar immune suppressive B cell sub-populations that can migrate into tumor deposits and acquire an immune suppressive phenotype, which then leads to attenuation of the local anti-tumor immune response. Other murine models of viral or chemically induced skin carcinogenesis have identified a pivotal role for B cells in promoting inflammation and carcinogenesis. While many human solid tumors demonstrate significant B cell infiltration and/or tertiary lymphoid structure formation, the functional properties of tumor-infiltrating B cells and their effects on immunity are poorly understood. Recent successes in early Phase I/II trials using anti-checkpoint inhibitor antibodies such as nivolumab or pidilizumab directed against PD-1 in the setting of Hodgkin's and non-Hodgkin's lymphomas validate the therapeutic utility of reversing B cell-mediated immune suppression. Further studies to define Breg subsets, and mechanisms of suppression, may provide new avenues for modulation of the immune response and meaningful therapeutic intervention in both lymphoid and solid tumors.

Human regulatory B cells in health and disease: therapeutic potential

“…To treat diseases such as RA, it is crucial that the Bregs migrate to the inflamed joints. While there is some evidence from murine studies showing that Bregs migrate to sites of inflammation (65), this requires further evaluation. It must be noted that while in vitro culture studies provide an indication of Breg function in vivo, they are not truly representative of Bregs at the site of inflammation.…”

“…More recently, it has been suggested that tumor-infiltrated B cells develop immune-suppressive properties via enhanced expression of TGF-β, PD-L1, CD86, and IL-10 (65). In this model, tumor-infiltrating B cells that were not initially intrinsically suppressive developed a Breg phenotype upon exposure to the tumor microenvironment (65). Some of the identified factors promoting a Breg phenotype are tumor-derived metabolites of 5-lipoxygenase in a breast cancer model, and placental growth factor (PIGF) in gliomas (66,67).…”

B Cells Promote Pancreatic Tumorigenesis

“…Interestingly, depleting B cells with anti-CD20 monoclonal antibody (mAb) alone does not inhibit tumor progression, but improves response in combination with chemotherapy ( 5 ). One suggested mechanism for TIL-B enhancement of tumor progression is through a subset of B cells that are suppressive, thereby inhibiting the antitumor immune responses ( 6 ). Similarly, in a transgenic metastatic, castration-resistant prostate cancer model ( 7 ), progression of the disease is associated with immune infi ltrates, including B cells, which are recruited to the tumor by the chemokine CXCL13.…”

Rôle protumoral des lymphocytes B dans le cancer du pancréas

“…Longtemps négligé, le rôle des LB (lymphocytes B) reste débattu. Si leur présence dans le microenvironnement tumoral est associée à un meilleur pronostic dans de nombreux cancers, elle peut aussi favoriser la progression tumorale [2,3]. Trois articles publiés en 2016 dans la revue Cancer Discovery décrivent le rôle protumoral des LB dans le cancer du pancréas le plus répandu, l'adé-nocarcinome canalaire pancréatique ou PDAC (pancreatic ductal adenocarcinoma), qui touche les cellules épithéliales des canaux pancréatiques ( Figure 1).…”