Authors
Yu-Ting Jiang, Guang-Qi Li, Yu-Wen Zhou, Ze-Dong Jiang, Yu-Nuo Zhao, Yu Zhang, Xiao-Meng Yin, Shen Li, Huan Tong, Lu-Si Feng, Shi-Yu Wen, Xue-Yan Zhou, Ren-Wei Li, Jing-Wen Wei, Jie-Ping Qiu, Yu-Hao Wei, Ke-Qin Tan, Sheng-Xin Zhang, Hao-Rui Zhou, Jia-Qing Yang, Jing Bai, Qin Deng, Xing-Gang Yang, Xiao-Qian Yang, Yu-Sha Wang, Xia-Wei Wei, Meng Qiu, Juan Huang, Xue-Lei Ma
Published in
Cell host & microbe. Oct 16, 2026. Epub Oct 16, 2026.
Abstract
Approximately 85% of colorectal cancers (CRCs) are microsatellite stable (MSS) and thus exhibit intrinsic resistance to anti-programmed death-1 (PD-1) therapy. In this study, we demonstrate that oral administration of Akkermansia muciniphila (Akk) suppresses tumorigenesis and reprograms the tumor microenvironment in MSS CRC mouse models. Akk attenuates macrophage efferocytosis through the TLR2/NF-κB pathway, an effect that leads to the accumulation of apoptotic cancer cells, which activates the cGAS-STING pathway and potentiates type I interferon production. This immunostimulatory cascade activates effector CD8+ T cells and enhances the response to anti-PD-1 therapy. We conducted a phase 1 trial (NCT06865521) combining Akk probiotics with PD-1 antibody in patients with metastatic MSS CRC after ≥1 prior line of therapy. The combination therapy was safe and achieved an objective response rate of 19%, with responders exhibiting enhanced antitumor immunity. Our multilevel investigation provides a promising strategy to overcome immunotherapy resistance in MSS CRC through targeted modulation of the gut microbiome.
PMID:
42887494
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.
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