TGFß in T cell biology and tumor immunity: Angel or devil?

ABSTRACT

The evolutionally conserved transforming growth factor ß (TGFß) affects multiple cell types in the immune system by either stimulating or inhibiting their differentiation and function. Studies using transgenic mice with ablation of TGFß or its receptor have revealed the biological significance of TGFß signaling in the control of T cells. However, it is now clear that TGFß is more than an immunosuppressive cytokine. Disruption of TGFß signaling pathway also leads to impaired generation of certain T cell populations. Therefore, in the normal physiological state, TGFß actively maintains T cell homeostasis and regulates T cell function. However, in the tumor microenvironment, TGFß creates an immunosuppressive milieu that inhibits antitumor immunity. Here, we review recent advances in our understanding of the roles of TGFß in the regulation of T cells and tumor immunity.