HDAC5 inhibited the expression of suppressor of cytokine signaling 3 (SOCS3) through histone deacetylation of H3K9ac and H3K27ac, and subsequently, the repression of SOCS3 further negatively regulated the expression of CCL2 and positively enabled the conversion from neutrophils to CCR2+ macrophages, which in turn provided support for the proliferation of cancer cells through KRAS mutations independent of transforming growth factor‐beta 1 (TGF‐β)/SMAD4. Here, CCL2 is linked to cancer.