Enhancing anti-tumor immunity and preventing tumor escape are efficient strategies to increase the efficacy of therapeutic cancer vaccines. However, the treatment of advanced tumors remains difficult, mainly due to the immunosuppressive tumor microenvironment. Regulatory T cells and myeloid-derived suppressor cells have been extensively studied, and their role in suppressing tumor immunity is now well established. In contrast, the role of B lymphocytes in tumor immunity remains unclear because B cells can promote tumor immunity or display regulatory functions to control excessive inflammation, mainly through IL-10 secretion. Here, in a mouse model of HPV-related cancer, we demonstrate that B cells accumulated in the draining lymph node of tumor-bearing mice, due to a prolonged survival, and showed a decreased expression of MHC class II and CD86 molecules and an increased expression of Ly6A/E, PD-L1 and CD39, suggesting potential immunoregulatory properties. However, B cells from tumor-bearing mice did not show an increased ability to secrete IL-10 and a deficiency in IL-10 production did not impair tumor growth. In contrast, in B cell-deficient μMT mice, tumor rejection occurred due to a strong T cell-dependent anti-tumor response. Genetic analysis based on single nucleotide polymorphisms identified genetic variants associated with tumor rejection in μMT mice, which could potentially affect reactive oxygen species production and NK cell activity. Our results demonstrate that B cells play a detrimental role in anti-tumor immunity and suggest that targeting B cells could enhance the anti-tumor response and improve the efficacy of therapeutic cancer vaccines.What's new?
Subsets of regulatory T-cells and myeloid-derived suppressor cells serve influential roles in tumor-mediated immunosuppression and are of special interest in the development of novel antitumor immunotherapies. By comparison, little is known about the role of B cells in tumor immunity. Here, B cells overexpressing PD-L1, CD39 and Ly6A/E were found to promote tumor growth in an E6/E7-expressing TC-1 mouse model of cervical cancer. The B cells operated in an IL-10-independent manner. In μMT mice, the absence of B cells was associated with efficient antitumor T-cell responses. The findings suggest that in the tumor microenvironment, B-cell responses hamper antitumor immunity.