Correlated expression of MYBL2 and CCL5 defines an immunosuppressive microenvironment and predicts poor prognosis in intrahepatic cholangiocarcinoma

Background The tumor immune microenvironment critically influences progression and therapeutic response in intrahepatic cholangiocarcinoma (ICC). MYBL2 drives tumor aggressiveness, while CCL5 regulates immune-cell recruitment; however, their combined impact on immune composition and PD-1 therapy response remains undefined. Methods Tumor specimens from 127 ICC patients were assessed by immunohistochemistry and whole-slide digital quantification. MYBL2 and CCL5 expression were classified into four combinatorial phenotypes. Associations with immune-cell infiltration, survival, and treatment response were evaluated using correlation analysis, Kaplan–Meier curves, Cox regression, and PD-1 interaction analyses. Seventy patients received adjuvant PD-1 therapy. Results MYBL2 and CCL5 expression were positively correlated ( r = 0.38, p < 0.001). Higher CCL5 levels were associated with increased CD163⁺ TAM density ( r = 0.31, p < 0.001) and a reduced CD8/CD163 ratio, indicating an immunosuppressive microenvironment. The MYBL2–CCL5 classification provided clear prognostic discrimination, with the Double-High subgroup showing the shortest OS and PFS. Among PD-1–treated patients, treatment benefit varied markedly across phenotypes: the Double-Low group achieved the greatest survival advantage, whereas the Double-High group showed minimal response, reflecting primary resistance. In multivariable analysis, Double-Low remained strongly protective compared with Double-High. Conclusion The MYBL2–CCL5 co-expression phenotype identifies an immunosuppressive, TAM-dominant microenvironment and serves as a dual biomarker for both prognosis and PD-1 treatment sensitivity in ICC. This immunologic classification offers a practical framework for postoperative risk stratification and personalized immunotherapy decision-making.