Tumor-associated regulatory T cells (Tregs), which restrain autoimmune reactions in healthy tissues, are generally associated with adverse outcomes across cancers. In colorectal cancers (CRCs), however, increased numbers of intratumoral Tregs have been linked to improved survival. Researchers co-led by Ludwig MSK’s Alexander Rudensky and Xiao Huang with MSK colleague Christina Leslie reported in a December issue of Immunity that this is because two subtypes of Tregs in CRC tumors, defined by their expression of immunomodulatory cytokine IL-10, have opposing effects on the cancer’s progression in mouse models. Found mainly in tissue adjacent to the tumor, IL-10+ Tregs suppress the production of IL-17—an interleukin that drives tumor growth—by Th17 T cells. Meanwhile, IL-10– Tregs, which are found within tumors, drive tumor growth by inhibiting the anti-tumor activity of cytotoxic T cells. The opposing effects of IL-10+/- Tregs on outcomes are reflected in human CRCs. A meta-analysis of single-cell gene expression datasets revealed that similar Tregs are present in lung, stomach and skin cancers. Further, IL-10– Tregs express CCR8, suggesting they might be depleted by antibodies to CCR8—a target already under evaluation in several clinical trials for cancer therapy. The functional differences between the two types of Tregs could permit selective targeting of pro-tumoral Treg cells while preserving the anti-tumor variety.
Opposing functions of distinct regulatory T cell subsets in colorectal cancer
Immunity, 2025 December 15