CD8A and cancer: This paradoxical expression pattern can be mechanistically explained by three key factors: 1) Metabolic microenvironment dependency - NPC1’s cholesterol transport function is particularly critical in cancers with high lipid metabolic demands (e.g., pancreatic adenocarcinoma), where it modulates immunosuppressive tumor microenvironments by sequestering cholesterol from CD8+ T cells (Zi et al., 2025).