TGF-β in T Cell Biology: Implications for Cancer Immunotherapy

Transforming Growth Factor beta (TGF-beta) is a pleiotropic cytokine produced in large amounts within cancer microenvironments that will ultimately promote neoplastic progression, notably by suppressing the host's T-cell immunosurveillance. This effect is mostly due to the well-known inhibitory effect of TGF-beta on T cell proliferation, activation, and effector functions. Moreover, TGF-beta subverts T cell immunity by favoring regulatory T-cell differentiation, further reinforcing immunosuppression within tumor microenvironments. These findings stimulated the development of many strategies to block TGF-beta or its signaling pathways, either as monotherapy or in combination with other therapies, to restore anti-cancer immunity. Paradoxically, recent studies provided evidence that TGF-beta can also promote differentiation of certain inflammatory populations of T cells, such as Th17, Th9, and resident-memory T cells (Trm), which have been associated with improved tumor control in several models. Here, we review current advances in our understanding of the many roles of TGF-beta in T cell biology in the context of tumor immunity and discuss the possibility to manipulate TGF-beta signaling to improve cancer immunotherapy.