CALB2 mediates tumor progression and immune escape in colorectal cancer by shaping an inhibitory immune microenvironment

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, characterized by a highly immunosuppressive tumor microenvironment (TME) that facilitates immune evasion and tumor progression. Methods: Integrated analysis of TCGA and GEO datasets was performed to evaluate CALB2 expression and its prognostic significance in CRC. Functional experiments including proliferation, migration, colony formation, and apoptosis assays were conducted following CALB2 knockdown. Co-culture assays and multiplex immunohistochemistry (mIHC) were used to assess TME remodeling. Results: T cell cytotoxicity, and reducing immunosuppressive cell infiltration. Mechanistically, CALB2 activated the STAT3 signaling pathway to promote CCL5 secretion, facilitating M2 polarization of macrophages and activation of fibroblasts. Conclusion: Our findings identify CALB2 as a critical regulator of tumor progression and immune escape in CRC, acting through dual oncogenic and immunomodulatory mechanisms. CALB2 represents a promising therapeutic target for enhancing immunotherapy efficacy in CRC.