The Role and Research Progress of CCR8-positive Regulatory T Cells in the Immune Microenvironment of Colorectal Cancer

Corresponding author: GONG Ping, 108797888@qq.com

DOI: 10.12201/bmr.202606.00048

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  Abstract: In colorectal cancer , patients with microsatellite-stable tumors respond poorly to immune checkpoint inhibitors , primarily due to the highly immunosuppressive nature of the tumor immune microenvironment. Regulatory T cells (Tregs) are key suppressive cells within the TIME. CCR8 is specifically and highly expressed on tumor-infiltrating Tregs, while its expression on peripheral Tregs and conventional T cells is extremely low, making it an ideal selective therapeutic target. CCR8? Tregs maintain the immunosuppressive state of the TIME by inhibiting CD8? cytotoxic T cells and Th1 immune responses, as well as modulating dendritic cell function. The infiltration level of CCR8? Tregs in CRC tissues is significantly positively correlated with TNM stage, lymph node metastasis, and poor prognosis. Monoclonal antibodies targeting CCR8 can selectively deplete intratumoral Tregs, thereby restoring anti-tumor immunity, and exhibit synergistic effects when combined with PD-1 blockade in preclinical models. Therefore, CCR8? Tregs are key drivers of immune evasion in CRC, and CCR8-targeting strategies hold promise to overcome the immunotherapy bottleneck in MSS CRC, offering broad clinical prospects.

  Key words: Colorectal cancer; Tumor immune microenvironment; Regulatory T cells; CCR8; Targeted therapy

  Submit time: 12 June 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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