Agents such as programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CLTA-4) inhibitors, in combination or as monotherapy, are finding increasing use as first-line agents for patients with R/M HNSCC. The gene discussed is CD274; the disease is head and neck squamous cell carcinoma.