To elucidate the therapeutic potential of dual PI3Kγ/PD-L1 inhibition in HNSCC, we orthotopically injected MOC2 cells into the right buccal mucosa of immunocompetent C57BL/6 mice and treated them with anti-PD-L1, IPI-549, anti-PD-L1 + IPI-549, or vehicle control. This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.