Mechanisms of T-cell inhibition: implications for cancer immunotherapy

Abstract

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.

Keywords::

• CTLA-4
• immune regulation
• immunotherapy myeloid-derived suppressor cells
• PD-1
• regulatory T cells
• T cells

Acknowledgements

The authors would like to thank James Allison for his critical review of this manuscript.

Financial & competing interests disclosure

Padmanee Sharma has served as a consultant on advisory boards for Bristol Myers-Squibb. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.