CD8A and neoplasm: TIM-3 can be expressed on activated CD4+ Th1 cells, mediating immune inhibition.56–58 On tumor-specific exhausted CD8+ T cells, expression of TIM-3 is upregulated.59 Galectin-9, carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), high mobility group box protein 1 (HMGB1), and phosphatidylserine have been identified as ligands of TIM-3 but none of them seems exclusive (Fig. 2).