CD8A and cancer: Multiple mechanisms are illustrated: (1) ligand–receptor crosstalk, Cells in the TME secrete multiple ligands that can be sensed by cancer cells or other cells, leading to the alteration of specific signaling pathways; (2) cell–cell interaction, such as the interaction between cytotoxic effector CD8+ T cells and tumor cells; and (3) cancer cells experiencing stress from the TME, such as hypoxia, starvation, and DNA damage (Maley et al., 2017).