KCTD10 promoting PD-L1 expression in colorectal cancer enhanced the anti-tumor effect of PD-1 antibody.

Integr Biol (Camb)

The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Science, Hunan Normal University, No. 36, Lushan Road, Yuelu District, Changsha 410081, China.

Published: January 2025


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Article Abstract

Colorectal cancer is a highly prevalent malignant tumor of the digestive tract worldwide. Immunotherapy has emerged as a critical therapeutic approach for CRC patients. We observed that KCTD10 expression is significantly downregulated in colorectal cancer tissues compared to normal tissues, and patients with higher KCTD10 expression exhibited prolonged survival. To investigate its functional role, we established stable KCTD10-overexpressing CT26 and SW480 colorectal cancer cell lines. Both in vitro and in vivo experiments demonstrated that KCTD10 overexpression suppresses colorectal cancer progression and inhibits the EMT process. Notably, KCTD10 overexpression upregulated PD-L1 expression and synergistically enhanced the therapeutic efficacy of anti-PD-1 treatment. Our findings reveal that KCTD10 functions as a tumor suppressor in colorectal cancer pathogenesis. Mechanistically, KCTD10 potentiates the antitumor efficacy of anti-PD-1 immunotherapy by upregulating PD-L1 expression, thereby proposing a novel therapeutic target and suggesting a promising combination strategy for CRC treatment. Insight box KCTD10 can inhibit the development of colorectal cancer and the EMT process. And the over-expression of KCTD10 increased the expression of PD-L1, improved the efficacy of PD-1 treatment.

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http://dx.doi.org/10.1093/intbio/zyaf014DOI Listing

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