There are four ligands capable of interacting with the IgV domain of TIM-3: HMGB1, the aforementioned nuclear protein released by necrotic cells; galectin-9 (Gal-9), a plasma and nuclear glycoprotein involved in signal transduction processes and in numerous aspects of tumor progression [20]; the adhesion molecule of carcinoembryonic antigen cells (carcinoembryonic antigen cell adhesion molecule or Ceacam-1), expressed on activated T lymphocytes [21]; phosphatidyl serine (PtdSer) exposed on the membranes of apoptotic cells [21]. This evidence concerns the gene HMGB1 and neoplasm.