Mechanisms of induction of regulatory B cells in the tumour microenvironment and their contribution to immunosuppression and pro-tumour responses

This article describes the induction of regulatory B cells in the tumour microenvironment. We discuss different phenotypes of Bregs and their mechanisms of suppression of anti-tumour responses. We also discuss the therapeutic implications of inhibition of Bregs in cancer. The presence of tumour-infiltrating immune cells was originally associated with the induction of anti-tumour responses and good a prognosis. A more refined characterization of the tumour microenvironment has challenged this original idea and evidence now exists pointing to a critical role for immune cells in the modulation of anti-tumour responses and the induction of a tolerant pro-tumour environment. The coordinated action of diverse immunosuppressive populations, both innate and adaptive, shapes a variety of pro-tumour responses leading to tumour progression and metastasis. Regulatory B cells have emerged as critical modulators and suppressors of anti-tumour responses. As reported in autoimmunity and infection studies, Bregs are a heterogeneous population with diverse phenotypes and different mechanisms of action. Here we review recent studies on Bregs from animal models and patients, covering a variety of types of cancer. We describe the heterogeneity of Bregs, the cellular interactions they make with other immune cells and the tumour itself, and their mechanism of suppression that enables tumour escape. We also discuss the potential therapeutic tools that may inhibit Bregs function and promote anti-tumour responses.