Importantly, our findings indicated that macrophage-specific Act1 knockdown activates STAT3 transcription factors to crosstalk with CRC cells and CD8+ T cells via CXCL9/10-CXCR3 and PD-1/PD-L1 axis respectively, and consequently promotes epithelial-mesenchymal transition and CRC progression. The gene discussed is PDCD1; the disease is colorectal carcinoma.