MSK Researchers Solve a Key Colorectal Cancer Mystery

Cancer research · Colorectal cancer

The study found that in colorectal cancer, regulatory T (Treg) cells have two distinct subtypes: IL‑10‑positive Tregs that restrain tumor growth by dampening Th17 activity, and IL‑10‑negative Tregs that suppress CD8+ T cells and promote tumor growth. Targeting the surface marker CCR8, which is highly expressed on the harmful IL‑10‑negative Tregs, could selectively deplete these cells while preserving the protective IL‑10‑positive Tregs, offering a new strategy to improve immunotherapy for most colorectal cancer patients.

A study by Memorial Sloan Kettering Cancer Center investigators demonstrates that a high density of regulatory T cells in colorectal cancer predicts better survival because these cells segregate into two subsets: IL‑10‑positive Tregs that inhibit tumor-associated Th17 cells and restrain tumor growth, and IL‑10‑negative Tregs that suppress CD8+ cytotoxic T cells and accelerate tumor growth. Targeted depletion of the IL‑10‑negative, CCR8‑expressing Tregs could therefore enhance anti‑tumor immunity without compromising beneficial Tregs.

Colorectal cancer is largely refractory to checkpoint‑inhibitor immunotherapy, yet a high infiltrate of regulatory T cells has been paradoxically linked to improved outcomes. By distinguishing between protective and harmful Treg subsets and identifying CCR8 as a selective target, this research provides a mechanistic basis for developing therapies that could redirect the immune response in the majority of colorectal cancer patients and potentially in other barrier‑tissue cancers.

Evidence level: Korai humán adat. Kis vagy feltáró emberi adat.

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