Depending on tumor characteristics (e.g., PD-L1 or PD-1 expression on tumor cells for anti-PD-1 mAb11–13, HMGB1 and LC3B for immunogenic chemotherapy14, or tumor microenvironment hallmarks such as IDO expression15, macrophage density16, tumor-infiltrating lymphocytes [TIL], or Th1 fingerprints17), one might envisage more specific and individualized I-O clinical management strategies. This evidence concerns the gene HMGB1 and neoplasm.