BackgroundColorectal 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.MethodsIntegrated 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.ResultsElevated CALB2 expression correlated significantly with poor prognosis in CRC patients. CALB2 knockdown suppressed CRC cell proliferation, migration, and colony formation, while promoting apoptosis.
CALB2 silencing also reprogrammed TME by inducing macrophage M1 polarization, enhancing CD8+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.ConclusionOur 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.
Frontiers in Immunology published a clinical update in Infectious Disease on 15 Apr 2026. The item focuses on CALB2 mediates tumor progression and immune escape in colorectal cancer by shaping an inhibitory immune microenvironment. Open the detail page to review the full original feed content.