The co-operation of cancer cells and supporting immune cells facilitates tumor development via the RAGE-activated expression of inflammatory cytokines, such as interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), other cytokines, chemokines, and exosomal microRNA [24,25,26,27], which, in turn, trigger the release of pro-inflammatory RAGE ligands, including HMGB1 and S100 family proteins [28,29,30,31]. The gene discussed is HMGB1; the disease is cancer.