B Cell Regulation of Antitumor Response

While the role of CD4+ T cells, cytolytic T cells, natural killer cells, and Th1 response in antitumor immunity has been appreciated for decades, a variety of human and murine tumors are heavily infiltrated with cells of B cell lineage. In contrast to the well-characterized role of T cells and adaptive immunity and of NK cells and the innate response in tumor rejection, as well as the suppressive role played by T-regulatory cells (Tregs), the role of B cells in the regulation of antitumor immunity is poorly understood. Increasing evidence points to a potential role of B cells in the suppression of immune responses in the context of malignancy. This includes a variety of murine models in which B cell infiltration has been associated with increased tumor growth, and even carcinogenesis, and the identification of subsets of B cells with unique regulatory properties. Several mechanisms have been implicated in B cell-mediated regulation of immune response. This includes preferential polarization of B cells along Th1 or Th2 pathways, the elaboration of immunosuppressive cytokines such as TGF-β and interleukin-10, B cell display of immunosuppressive co-stimulatory ligands such as CD86 and PD-L1, and/or B cell support for the development of Tregs within the tumor microenvironment. Evidence is also accumulating that malignant lymphoma and leukemia B cells may distort the balance between Tregs and so-called Th17 cells leading to a tumor microenvironment that is more conducive to lymphoma growth.