biostudies-literatureUnknown21(8)Wang JThe presence of tumor-associated macrophages (TAMs) characterized by an M2-like phenotype sustains a robust immunosuppressive tumor microenvironment (TME), promoting liver hepatocellular carcinoma (LIHC) progression. Here, we find that genetic deletion of cyclophilin J (CYPJ) in mice significantly accelerates the development of liver cancer. Analysis of immune cell infiltration reveals that high expression of CYPJ correlates with an increased proportion of M1-polarized, anti-tumor macrophages and CD8⁺ T cells in the TME. Mechanistically, we demonstrate that CYPJ interacts with AKT1 and inhibits the PI3K-AKT signaling pathway, which leads to polarization of TAMs toward the anti-tumor M1 phenotype, resulting in a tumor-suppressive effect. Collectively, our findings implicate CYPJ International journal of biological sciences3776-3790https://www.ebi.ac.uk/biostudies/studies/S-EPMC12160919biostudies-literatureCyclophilin J Reprograms Tumor-associated Macrophages to Exert an Anti-tumor Effect in Liver Cancer.PMC12160919Zeng QYao CFu LPeng LZhang SChen SSheng CWang JMao YfalseCyclophilin J Reprograms Tumor-associated Macrophages to Exert an Anti-tumor Effect in Liver Cancer.The presence of tumor-associated macrophages (TAMs) characterized by an M2-like phenotype sustains a robust immunosuppressive tumor microenvironment (TME), promoting liver hepatocellular carcinoma (LIHC) progression. Here, we find that genetic deletion of cyclophilin J (CYPJ) in mice significantly accelerates the development of liver cancer. Analysis of immune cell infiltration reveals that high expression of CYPJ correlates with an increased proportion of M1-polarized, anti-tumor macrophages and CD8⁺ T cells in the TME. Mechanistically, we demonstrate that CYPJ interacts with AKT1 and inhibits the PI3K-AKT signaling pathway, which leads to polarization of TAMs toward the anti-tumor M1 phenotype, resulting in a tumor-suppressive effect. Collectively, our findings implicate CYPJ 2025-01-01T00:00:00Z20252026-07-15T06:19:52.495Z2026-06-30T03:21:06.959ZS-EPMC121609194052000210.7150/ijbs.113197