Harnessing the biology of regulatory T cells to treat disease

Abstract

Regulatory T (Treg) cells are a suppressive subset of CD4+ T cells that maintain immune homeostasis and restrain inflammation. Three decades after their discovery, the promise of strategies to harness Treg cells for therapy has never been stronger. Multiple clinical trials seeking to enhance endogenous Treg cells or deliver them as a cell-based therapy have been performed and hint at signs of success, as well as to important limitations and unanswered questions. Strategies to deplete Treg cells in cancer are also in active clinical testing. Furthermore, multi-dimensional methods to interrogate the biology of Treg cells are leading to a refined understanding of Treg cell biology and new approaches to harness tissue-specific functions for therapy. A new generation of Treg cell clinical trials is now being fuelled by advances in nanomedicine and synthetic biology, seeking more precise ways to tailor Treg cell function. This Review will discuss recent advances in our understanding of human Treg cell biology, with a focus on mechanisms of action and strategies to assess outcomes of Treg cell-targeted therapies. It highlights results from recent clinical trials aiming to enhance or inhibit Treg cell activity in a variety of diseases, including allergy, transplantation, autoimmunity and cancer, and discusses ongoing strategies to refine these approaches. Regulatory T cells keep the immune system in check to maintain homeostasis and restrain inflammation. This Review discusses strategies to harness these cells therapeutically for autoimmunity, transplant tolerance or cancer, for example, by boosting their endogenous function, depleting them or administering them as engineered cell-based therapies.