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Managing Regulatory T Cells to Improve Cancer Immunotherapy

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Cancer Immunotherapy

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Abstract

Regulatory T cells (Tregs) are increased in peripherally circulating blood cells and in the solid tumor masses of patients afflicted with many different cancer histologies. Cancer Tregs not only are capable of impeding endogenous protective anti-tumor immunity from optimal functioning but are also capable of impeding the efficacy of anti-cancer immunotherapy. Tumor-associated Tregs represent heterogeneous populations, differing by their origins and in their mechanisms used to impede anti-tumor immunity. Their properties can differ compared to those in peripheral circulation. Most studies now report that Treg content in the tumor inversely correlates with survival or therapeutic response, but a few reports suggest that Tregs are beneficial to patients with certain types of cancers. Therapeutic strategies to manage Treg capacity to mediate immune dysfunction include depletion, regulatory functional blockade, differentiation blockade, altering trafficking, differentiation diversion, or raising the threshold of anti-cancer effector cells for Treg-mediated regulation. Several clinical trials have shown the feasibility and relative safety of managing Tregs in human cancer, although treatment effects are modest. This chapter will review contemporary knowledge of Tregs in cancers, including origins, mechanisms of action, interactions with other immune cells and strategies for therapeutic management, addresses the major questions facing the field and suggests additional important areas for future research. The focus is on CD4+CD25+Foxp3+ Tregs, but other cancer-associated regulatory cells will be addressed in brief.

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Acknowledgements

I regret that space limitations preclude citing many important works from my colleagues. Thanks to Vincent Hurez, Lishi Sun, Mark Kious, Suzanne Thibodeaux, Kruthi Murthy, Srilaskmi Pandaswara, AiJie Liu, and Sara Ludwig for expert technical assistance. Suzanne Thibodeaux helped create graphics. This work was supported by CA105207, CA054174, FD003118, the Fanny Rippel Foundation, the Voelcker Trust, the Hayes Endowment, The Holly Beach Public Library Association, The Owens Foundation The Hogg Foundation and UTHSCSA endowments.

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    Tyler J. Curiel M.D., M.P.H.

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Curiel, T.J. (2013). Managing Regulatory T Cells to Improve Cancer Immunotherapy. In: Curiel, T. (eds) Cancer Immunotherapy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4732-0_9

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