Although TNFα and IFN‐γ have long been implicated in antitumor immune responses, recent reports suggested that they may also play pro‐tumorigenic roles through the development of an immunosuppressive TME.[40, 41] We found that HMGB1, in combination with IFN‐γ, synergistically promoted CXCL2 expression in MC38, CT26, and CRC tissues (Figure 7D), and HMGB1 in combination with TNFα also synergistically increased CXCL2 expression in CRC tissues (Figure 7D). This evidence concerns the gene DDX53 and colorectal carcinoma.