HMGB1 activates the MyD88/TRIF-dependent NF-κB pathway by binding to the RAGE and TLR2/4 receptors, which promotes the synthesis and release of core inflammatory mediators such as IL-6 and TNF-α by macrophages (185): IL-6 activates and maintains the inflammatory response, promotes T cell proliferation and differentiation, and enhances the immune response; TNF-α has antitumor activity, induces apoptosis of tumor cells, promotes infiltration of inflammatory cells, and enhances the killing of tumor cells by immune cells (186). Here, HMGB1 is linked to neoplasm.