ALK and neoplasm: Several different mechanisms have been proposed for CD274 upregulation in tumor cells: (1) innate intrinsic induction: constitutive oncogenic signaling within tumor cells, such as ALK and EGFR, that lead to elevated expression of CD274 (PD-L1)21,22; and (2) adaptive immune resistance: induction of CD274 (PD-L1) expression on tumor cells in response to local inflammatory signals produced by active immune response, such as CD8+ cytotoxic T lymphocytes23,24.