The PD-1/PD-L1 immune checkpoint signaling axis exhibits remarkable responses in platinum-refractory recurrent or metastatic HNSCC; PD-L1-containing TDEs, which transfer functional PD-L1 and inhibit immune responses, may be regulators and biomarkers of resistance to PD-1 blockade therapy. The gene discussed is CD274; the disease is head and neck squamous cell carcinoma.