Smad4 acts as a tumor suppressor in CRC; however, the role of Smad4-mediated signaling in the immune microenvironment of CRC remains controversial Smad4 deletion in human CRC cells resulted in the recruitment of more neutrophils through the CXCL1/8-CXCR2 axis to promote CRC progression 34. This evidence concerns the gene CXCL1 and neoplasm.