Mechanistically, CALB2 activated the STAT3 signaling pathway to promote CCL5 secretion, facilitating M2 polarization of macrophages and activation of fibroblasts.<h4>Conclusion</h4>Our findings identify CALB2 as a critical regulator of tumor progression and immune escape in CRC, acting through dual oncogenic and immunomodulatory mechanisms. The gene discussed is CCL5; the disease is colorectal carcinoma.