B cells in the tumor microenvironment: Multi-faceted organizers, regulators, and effectors of anti-tumor immunity

Abstract

Our understanding of tumor-infiltrating lymphocytes (TILs) is rapidly expanding beyond T cell-centric perspectives to include B cells and plasma cells, collectively referred to as TIL-Bs. In many cancers, TIL-Bs carry strong prognostic significance and are emerging as key predictors of response to immune checkpoint inhibitors. TIL-Bs can perform multiple functions, including antigen presentation and antibody production, which allow them to focus immune responses on cognate antigen to support both T cell responses and innate mechanisms involving complement, macrophages, and natural killer cells. In the stroma of the most immunologically "hot" tumors, TIL-Bs are prominent components of tertiary lymphoid structures, which resemble lymph nodes structurally and functionally. Additionally, TIL-Bs participate in a variety of other lympho-myeloid aggregates and engage in dynamic interactions with the tumor stroma. Here, we summarize our current understanding of TIL-Bs in human cancer, highlighting the compelling therapeutic opportunities offered by their unique tumor recognition and effector mechanisms.