Mechanisms of T-cell inhibition: implications for cancer immunotherapy

Cancer vaccines designed to augment effector T-cell responses have been disappointing with respect to clinical efficacy. This lack of effectiveness may be due to the fact that regulatory mechanisms, both intrinsic and extrinsic to activated T cells, play important roles in inhibiting vaccine-induced effector T-cell responses. This concept raises the possibility that blockade of these regulatory checkpoints might enhance anti-tumor immune responses. In this review, we discuss several regulatory mechanisms that act to control effector T-cell responses and identify strategies to circumvent these mechanisms in order to improve clinical responses.