Cell 180, 1081–1097.e24 (2020)

It is increasingly appreciated that B cells have an important influence on the progression of cancer. In Cell, Su and colleagues characterize the role of B cells in both human patients and mouse models of breast cancer before and after neoadjuvant chemotherapy. Treatment results in tumor cell death and release of complement proteins, which in turn signal via complement receptor 2 (CR2) on B cells within the tumor microenvironment, leading to their expression of the T cell costimulatory molecule ICOSL. The frequency of ICOSL+ B cells within the TME correlates with increased patient survival. Loss of ICOSL or CR2-mediated signaling on B cells impairs the antitumor response in mouse models of breast cancer. The complement-inhibiting molecule CD55 reduces the frequency of ICOSL+ B cells and can swing the response in favor of the tumor. Modulating the strength of complement signaling might therefore be a useful immunotherapeutic approach for breast cancer.