Taken together, our findings confirmed that Act1 downregulation in macrophages activates STAT3 to promote adenoma-adenocarcinoma transition via CXCL9/10-CXCR3-axis in CRC cells and immunosuppression via PD-l/PD-L1 axis in CD8+ T cells (Fig. 6). Here, CXCL9 is linked to colorectal carcinoma.