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Here, we identified surgery-induced C-C motif chemokine ligand 11 (CCL11) as a pivotal driver of HCC recurrence through dual mechanisms of immunosuppression and tumor invasiveness. Elevated postoperative circulating CCL11 levels correlated strongly with HCC recurrence and poorer survival, and their integration with clinical parameters enhanced the predictive accuracy of HCC recurrence. Mechanistically, hepatic injury-induced CCL11 recruited immunosuppressive CCR5\n                    <jats:sup>+<\/jats:sup>\n                    CD206\n                    <jats:sup>+<\/jats:sup>\n                    M2-like macrophages into the residual liver. These macrophages exhibited enhanced PD-L1 expression via activation of the CCL11\/IKK\/I\u03baB\/NF-\u03baB1 axis and promoted regulatory T cell (Treg) induction from na\u00efve CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Concurrently, CCL11-CCR3 signaling in HCC cells activated PI3K\/AKT\/MafK to upregulate MMP13, enhancing the invasion ability of HCC cells. In orthotopic models, CCL11 enrichment increased tumor burden and extrahepatic metastases, while post-resection anti-CCL11 therapy reduced HCC recurrence and extended the survival rate of tumor-bearing mice. Our findings unveil CCL11 as a master regulator of the pro-tumorigenic niche post-resection, driving recurrence through coordinated immune evasion and promoting tumor invasiveness. Targeting the CCL11-CCR5\/CCR3 axis presents a promising strategy to improve HCC surgical outcomes.\n                  <\/jats:p>","DOI":"10.1038\/s41419-026-08508-4","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T17:08:54Z","timestamp":1771520934000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CCL11 promotes hepatocellular carcinoma recurrence after surgery by potentiating immunosuppressive CCR5\u2009+\u2009CD206\u2009+\u2009M2-like macrophages and promoting tumor invasiveness"],"prefix":"10.1038","volume":"17","author":[{"given":"Jiaqi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar Wai-Ho","family":"Yeung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinuan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan To","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5663-6866","authenticated-orcid":false,"given":"Kwan","family":"Man","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9822-1335","authenticated-orcid":false,"given":"Kevin Tak-Pan","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"8508_CR1","first-page":"12","volume":"74","author":"RL Siegel","year":"2024","unstructured":"Siegel RL, Giaquinto AN, Jemal A. 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