Regulatory T cells and cancer

Abstract

Regulatory T cells (T reg) are key mediators of tumor immune suppression, and elevated T reg proportions have now been identified in association with all major types of human cancer. Suppression of antitumor immunity is mediated by both natural (nT reg) and induced T reg (iT reg) subsets, which express Foxp3, and they have been shown to engage a wide range of tumor-associated antigens. Preexisiting T reg are actively recruited to tumors through chemokine and cytokine signals and become activated by dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) within tumors. Th0 cells are also efficiently converted to Foxp3-expressing iT reg in response to TGF-β produced by tumor cells and antigen-presenting cells (APCs) in the tumor microenvironment. T reg exert suppression of tumor-specific T-cell responses through a variety of mechanisms including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), interleukin 35 (IL-35), interleukin 10 (IL-10), and transforming growth factor beta (TGF-β). Therapies that inhibit these pathways, or directly deplete T reg populations, are an effective means for enhancing antitumor immunity. Clinical trials are now beginning to reveal that blocking T reg responses is a necessary component of successful cancer immunotherapy.