CD8A and neoplasm: Various different mechanisms have been asserted for PD-L1 upregulation in tumor cells: (1) innate intrinsic induction—constitutive oncogenic signaling in tumor cells, such as ALK and EGFR, leading to overexpression of PD-L1; and (2) adaptive immune resistance—stimulation of PD-L1 expression in tumor cells in reply to local inflammatory signals produced by the active immune response, such as CD8 cytotoxic T lymphocytes [34].