FOXP3+ Treg as a therapeutic target for promoting anti-tumor immunity

Theresa L Whiteside ¹

Affiliations

¹ a Departments of Pathology, Immunology and Otolaryngology , University of Pittsburgh School of Medicine, UPMC Hillman Cancer Center , Pittsburgh , PA , USA.

PMID: 29532697
109 References
38 citations

Abstract

Regulatory T cells (Treg) characterized by expression of FOXP3 and strong immunosuppressive activity play a key role in regulating homeostasis in health and disease. Areas covered: Human Treg are highly diverse phenotypically and functionally. In the tumor microenvironment (TME), Treg are reprogrammed by the tumor, acquiring an activated phenotype and enhanced suppressor functions. No unique phenotypic markers for Treg accumulating in human tumors exist. Treg are heterogeneous and use numerous mechanisms to mediate suppression, which either silences anti-tumor immune surveillance or prevents tissue damage by activated T cells. Treg plasticity in the TME endows them with dual functionality. Treg frequency in tumors associates either with poor or improved survival. Treg responses to immune checkpoint inhibition (ICI) differ from the restorative effects ICIs induce in other immune cells. Therapies used to silence Treg, including ICIs, are only partly successful. Treg persistence and resistance to depletion are critical for maintaining homeostasis. Expert opinion: Treg emerge as a heterogeneous subset of immunosuppressive T cells, which usually, but not always, favor tumor progression. Treg are also engaged in non-immune activities that benefit the host. Therapeutic silencing of Treg in cancer requires a deeper understanding of Treg activities in human health and disease.

Keywords: Regulatory T cells (Treg); Treg and checkpoint inhibition; Treg phenotype; Treg suppressor functions; cancer; tumor microenvironment (TME).

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