Regulatory T cells in the tumour microenvironment.

Imianowski, Charlotte J; Chen, Qiang; Workman, Creg J; Vignali, Dario A A · Nat Rev Cancer · 2025

review · Level V

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Abstract

The powerful suppressive capabilities of regulatory T (T<sub>reg</sub>) 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 T<sub>reg</sub> cells while leaving the wider system unperturbed. It is also unknown whether therapies depleting or disrupting the function of tumour-infiltrating T<sub>reg</sub> cells will provide the greatest efficacy while limiting immune-related adverse events. In addition, T<sub>reg</sub> cells share much of their biology with conventional CD4<sup>+</sup> T cells, introducing challenges when designing targeted immunotherapies. In this Review, we discuss recent advances in differentiating tumour-infiltrating T<sub>reg</sub> cells from their systemic and tissue-resident counterparts and understanding how the biology of tumour-infiltrating T<sub>reg</sub> cells differs from conventional CD4<sup>+</sup> T cells. We also discuss how recent technological advances may enable the study of tumour-infiltrating T<sub>reg</sub> cells in even greater detail, helping to identify new targets for next-generation immunotherapeutic drugs.

Medical subject headings