Indeed, in the search of a better understanding of the mechanisms involved in the acquired immunotherapy resistance, it has been reported that the unresponsiveness to PD-1/PD-L1 inhibition in lung murine models is probably mediated by the tumor up-regulation of CD38 enzyme, which is induced by all-trans retinoic acid and IFN-β in the TME. This evidence concerns the gene PDCD1 and neoplasm.