biostudies-literatureZhang YNational Institutes of Health102589https://www.ebi.ac.uk/biostudies/studies/S-EPMC12923984biostudies-literatureUnknown7(2)Colorectal cancer mortality is primarily driven by hepatic metastasis, with 50-60% of patients relapsing following liver metastasis resection due to micro-metastases or tumor cell dissemination. Surgery-induced immunologic disturbances contribute to liver recurrence. Exercise modulates immune responses, yet its role in surgical stress-promoted liver metastasis remains unclear. We demonstrate that 4 weeks of preoperative exercise (PEx) limits tumor growth in a murine model of surgical stress-promoted liver metastasis by shifting Kupffer cells toward an anti-tumor phenotype. PEx promotes Kupffer cell cytotoxic cytokines release and enhances CD8⁺ T cells recruitment and activation via the CXCL9-CXCR3 axis. Elevated CXCL9 levels are observed in murine and patient sera post exercise,Cell reports. MedicinePreoperative exercise induces anti-tumor Kupffer cells to prevent surgical stress-promoted colorectal cancer liver metastasis.PMC12923984R01-CA214865R01-GM137203R01-GM95566Xia YBeane JLi JHuang HZhang HCao CShen CCummins KCWang HHamad AEl Moheb MZhang YWang YEjaz ATsung AfalsePreoperative exercise induces anti-tumor Kupffer cells to prevent surgical stress-promoted colorectal cancer liver metastasis.Colorectal cancer mortality is primarily driven by hepatic metastasis, with 50-60% of patients relapsing following liver metastasis resection due to micro-metastases or tumor cell dissemination. Surgery-induced immunologic disturbances contribute to liver recurrence. Exercise modulates immune responses, yet its role in surgical stress-promoted liver metastasis remains unclear. We demonstrate that 4 weeks of preoperative exercise (PEx) limits tumor growth in a murine model of surgical stress-promoted liver metastasis by shifting Kupffer cells toward an anti-tumor phenotype. PEx promotes Kupffer cell cytotoxic cytokines release and enhances CD8⁺ T cells recruitment and activation via the CXCL9-CXCR3 axis. Elevated CXCL9 levels are observed in murine and patient sera post exercise,2026-01-01T00:00:00Z2026 Feb2026-07-16T15:13:26.103Z2026-07-10T03:09:17.476ZS-EPMC129239844166692110.1016/j.xcrm.2026.102589