CD274 and neoplasm: Modulation of PD-L1 levels occurs via two major pathways, the intracellular (innate) signaling pathway mediated by PI3K/AKT/mTOR activation and/or the extracellular induced (adaptive) pathway mediated by IFNγ production by TILs and subsequent IFNGRs/JAK/STAT signaling in tumor cells [26].