Opposing Functions of Distinct Regulatory T Cell Subsets in Colorectal Cancer.

Publication Type	Preprint
Authors	Huang X, Feng D, Mitra S, Andretta E, Hooshdaran N, Ghelani A, Wang E, Frost J, Lawless V, Vancheswaran A, Jiang Q, Leslie C, Rudensky A
Journal	bioRxiv
Date Published	02/23/2025
ISSN	2692-8205
Abstract	Regulatory T (Treg) cells contribute to solid organ cancer progression, except in colorectal cancer (CRC) despite being abundantly present. Here, we demonstrate that two distinct tumoral IL-10⁺ and IL-10⁻ Treg cell subsets exert opposing functions by counteracting and promoting CRC tumor growth, respectively. The tumor restraining activity of IL-10⁺ Treg cells was mediated by their suppression of effector CD4 T cell production of IL-17, which directly stimulates CRC tumor cell proliferation. Consistently, IL-10⁻ Treg cells were more abundant in both mouse and human CRC tumors than in tumor-adjacent normal tissues, whereas IL-10+ Treg cells exhibited the opposite distribution. Furthermore, relative abundance of IL-10⁺ and IL-10⁻ Treg cells correlated with better and worse disease prognoses in human CRC, respectively. This functional dichotomy between Treg cell subsets provides a rationale for therapeutic strategies to selectively target pro-tumoral Treg cells while preserving their anti-tumoral counterparts across barrier tissue cancers that harbor both subsets.
DOI	10.1101/2025.02.07.637083
PubMed ID	39975175
PubMed Central ID	PMC11839124