To explore if IL4I1 signaling to CCL2 could mediate macrophages polarization, an indirect co-culture condition between si-IL4I1-transfected ccRCC cells (786-O and 769-P) and M0-like macrophages was conducted and revealed that silencing IL4I1 inhibited M2-like macrophages polarization associated with JAK1/STAT3 phosphorylation and downregulated CCL2 expression. The gene discussed is CCL2; the disease is nonpapillary renal cell carcinoma.