CD8A and neoplasm: Further, tumor cells can directly promote the formation of ICB-refractory exhausted CD8+ T cells (Tex) prior to treatment and exhaustion of effector cells after immunotherapeutic reinvigoration via persistent NeoAg display (similar to chronic viral infection) or secretion of immunosuppressive factors such as vascular endothelial growth factor-A (VEGF-A) (13–18).