Overall, in the treatment of HNSCC, PD-1/PD-L1 blockade may result in a further upregulation of the inhibitory checkpoints on the surface of TILs, thus supporting a circuit of compensatory signaling and potentially permitting immune escape from PD-1/PD-L1 blockade in the TME. The gene discussed is CD274; the disease is head and neck squamous cell carcinoma.