PLAN B for immunotherapy: Promoting and leveraging anti-tumor B cell immunity

Current immuno-oncology primarily focuses on adaptive cellular immunity mediated by T lymphocytes. The other important lymphocytes, B cells, are largely ignored in cancer immunotherapy. B cells are generally considered to be responsible for humoral immune response to viral and bacterial infections. The role of B cells in cancer immunity has long been under debate. Recently, increasing evidence from both preclinical and clinical research has shown that B cells can also induce potent anti-cancer immunity, via humoral and cellular immune responses. Yet it is unclear how to efficiently integrate B cell immunity in cancer immunotherapy. In the current perspective, anti-tumor immunity of B cells is discussed regarding antibody production, antigen presentation, cytokine release and contribution to intratumoral tertiary lymphoid structures. Afterwards, immunosuppressive regulatory phenotypes of B cells are summarized. Furthermore, strategies to activate and modulate B cells using nanomedicines and biomaterials are discussed. This article provides a unique perspective on "PLAN B" (promoting and leveraging anti-tumor B cell immunity) using nanomedicines and biomaterials for cancer immunotherapy. This is envisaged to form a new research direction with the potential to reach the next breakthrough in immunotherapy.