CD8A and neoplasm: However, one of the most important anti-tumor mechanisms, which affects the normal activity of TILs and also leads to the abnormal function of CD8+ TILs, is represented by the programmed Death-1 (PD-1) and its ligand, the Programmed Death Ligand 1 (PD-L1) axis, which are key coinhibitory immune-checkpoint regulators and deliver inhibitory signals that constrain T-cell activation, proliferation, and effector function, thereby maintaining peripheral tolerance and shaping anti-tumor immunity [34].