CD8A and neoplasm: The fact that single agent ICT or combinations of different ICBs targeting either receptors or ligands of T-cell inhibition pathways, can re-invigorate exhausted CD8+ T-cells by enhancing their anti-viral (286) or anti-tumor activity in various animal models and in humans (287) would suggest that not all exhausted CD8+ T-cells are terminally differentiated or dysfunctional.