[CEACAM4 promotes glioblastoma progression by regulating a myeloid cell-mediated immunosuppressive tumor microenvironment].

Objective To investigate the role and underlying mechanisms of carcinoembryonic antigen-related cell adhesion molecule 4 (CEACAM4) in the immunosuppressive microenvironment of glioblastoma (GBM), to clarify its impact on tumor progression and immune evasion, and to evaluate its potential as a prognostic biomarker and therapeutic target. MethodsCEACAM4 expression, prognostic significance, and immune infiltration profiles were analyzed using The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus(GEO) datasets. CEACAM4 knockdown glioma models were established using shRNA-mediated silencing. The effects of CEACAM4 on tumor cell proliferation, migration, cell cycle progression, and apoptosis were assessed through in vitro assays. Tumor cell-macrophage co-culture systems and xenograft models were used to evaluate the effects of CEACAM4 on myeloid cell recruitment, tumor-associated macrophage (TAM) polarization, and tumor growth in vivo. Results CEACAM4 was significantly upregulated in glioma tissues, particularly in IDH wild-type, 1p/19q non-codeleted, and high-grade tumors. High CEACAM4 expression was associated with poor overall survival. CEACAM4 silencing inhibited glioma cell proliferation, migration, induced G1 cell cycle arrest, and promoted apoptosis. Moreover, CEACAM4 deficiency reduced macrophage recruitment and suppressed TAM polarization toward the immunosuppressive M2 phenotype. Bioinformatics analysis revealed a positive correlation between CEACAM4 expression and immunosuppressive myeloid cell infiltration. In vivo, CEACAM4 knockdown suppressed tumor growth and decreased immunosuppressive myeloid cell accumulation. Conclusion CEACAM4 promotes glioma progression by enhancing malignant tumor phenotypes and shaping a myeloid cell-mediated immunosuppressive tumor microenvironment. CEACAM4 may serve as a prognostic biomarker and a potential therapeutic target for improving immunotherapy efficacy and overcoming treatment resistance in GBM.