In addition, tumor hypoxia and abundance of HMGB1 also triggers RAGE-dependent mechanisms, resulting in tumor hypoxic core retention of M2-macrophages [197], which plays a significant immunosuppressive role by secreting immunosuppressive molecules, such as IL-10, TGF-β, and human leukocyte antigen G within the TME [198]. This evidence concerns the gene HMGB1 and neoplasm.