Controversies on the role of Th17 in cancer: a TGF-β-dependent immunosuppressive activity?

The immune system has important roles in limiting the spread of cancer and shaping the tumor microenvironment. Although the contributions of T helper 17 (Th17) cells (a subtype of CD4(+) T lymphocytes) to autoimmunity and allergy response are well known, their roles in cancer remain ambiguous. Despite adoptive transfer studies indicating that mouse Th17 cells support anticancer immunity, the Th17 cells that naturally infiltrate experimental tumors appear to have a tumor-promoting effect. These contradictory properties can be related to the high degree of plasticity inherent in Th17 cells and their capacity to differentiate into tumoricidal Th1-like cells. Mouse Th17 cells induced by transforming growth factor-beta (TGF-beta) express CD39 and CD73 ectonucleotidases on their surfaces, which leads to adenosine release and suppression of T cell immunity. Here, we discuss how TGF-beta acts as a molecular switch controlling the immunoregulatory properties of Th17 cells.