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Review
. 2025 Sep;25(9):703-722.
doi: 10.1038/s41568-025-00832-9. Epub 2025 Jun 10.

Regulatory T cells in the tumour microenvironment

Charlotte J Imianowski #  1   2 , Qiang Chen #  1   2 , Creg J Workman  1   2 , Dario A A Vignali  3   4   5
Affiliations
Review

Regulatory T cells in the tumour microenvironment

Charlotte J Imianowski et al. Nat Rev Cancer. 2025 Sep.

Abstract

The powerful suppressive capabilities of regulatory T (Treg) cells and their appreciable contribution to tumour progression make them attractive immunotherapeutic targets. However, their role in systemic immune homeostasis makes it important to find ways to specifically target tumour-infiltrating Treg cells while leaving the wider system unperturbed. It is also unknown whether therapies depleting or disrupting the function of tumour-infiltrating Treg cells will provide the greatest efficacy while limiting immune-related adverse events. In addition, Treg cells share much of their biology with conventional CD4+ T cells, introducing challenges when designing targeted immunotherapies. In this Review, we discuss recent advances in differentiating tumour-infiltrating Treg cells from their systemic and tissue-resident counterparts and understanding how the biology of tumour-infiltrating Treg cells differs from conventional CD4+ T cells. We also discuss how recent technological advances may enable the study of tumour-infiltrating Treg cells in even greater detail, helping to identify new targets for next-generation immunotherapeutic drugs.

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Conflict of interest statement

Competing interests: D.A.A.V. and C.J.W. have patents covering LAG3, with others pending, and are entitled to a share of net income generated from licensing of these patent rights for commercial development. D.A.A.V. is a cofounder and stockholder of Novasenta, Potenza, Tizona and Trishula; a stockholder of Werewolf; has patents licensed and royalties for BMS and Novasenta; a scientific advisory board member of Werewolf, Apeximmune and T7/Imreg Bio; a consultant for BMS, Regeneron, Ono Pharma, Peptone, Avidity Partners, Third Arc Bio, Peptone, Secarna and Curio Bio; and has been provided funding from BMS and Novasenta. C.J.I. and Q.C. declare no competing interests.

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