In general, interleukins like IL-2, IL-12, IL-21 facilitate M1 polarization [86], while M0 macrophages polarize into M2-like phenotype via the stimulation of cytokines and chemokines such as CCL2 and VEGF in HCC [87, 88], IL-4/13 in various cancers, IL-6 in HCC [89], breast cancer [55], CRC [90] and GBM [91], IL-8 in pancreatic cancer [82], lung cancer [92] and esophageal squamous cell carcinoma [93], IL-10 in CRC [79] and gastric cancer [94], IL-33 in esophageal squamous cell carcinoma [95], gastric cancer [96], lung cancer [97] and CRC [98], IL-34 in breast cancer [99] and HCC [100]. The gene discussed is IL21; the disease is hepatocellular carcinoma.