The increased detection of Akt-1 in co-immunoprecipitation with PD-L1 in HNSCC cell lines, along with the recent description of the intracellular signalosome of PD-L1, highlight how it functions immune-independently, regulated by the mTOR-Akt pathway [37,129], which could explain the impact of the intrinsic functions of PD-L1 on the cellular processes that culminate in the sustained proliferation and growth of cancer cells. This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.