TGF-β and Cancer Immunotherapy.

The cytokine, transforming growth factor beta (TGF-β), has a history of more than 40 years. TGF-β is secreted by many tumor cells and is associated with tumor growth and cancer immunity. The canonical TGF-β signaling pathway, SMAD, controls both tumor metastasis and immune regulation, thereby regulating cancer immunity. TGF-β regulates multiple types of immune cells in tumor microenvironment, including T cells, natural killer (NK) cells, and macrophages. One of the main roles of TGF-β in the tumor microenvironment is the generation of regulatory T cells, which contribute to the suppression of anti-tumor immunity. Because cancer is one of the highest causes of death globally, the discovery of immune checkpoint inhibitors by Honjo and Allison in cancer immunotherapy earned a Nobel Prize in 2018. TGF-β also regulates the levels of immune checkpoints inhibitory receptors on immune cells. Immune checkpoints inhibitors are now being developed along with anti-TGF-β antibody and/or TGF-β inhibitors. More recently, chimeric antigen receptors (CARs) were applied to cancer immunity and tried to combine with TGF-β blockers.