The major immune checkpoint pathways implicated in HNSCC immunosuppression are PD-1/PD-L1, cytotoxic T lymphocyte antigen 4 (CTLA-4), the T-cell immunoglobulin mucin 3 (TIM-3), the lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (TIGIT) (Figure 1). The gene discussed is CD274; the disease is head and neck squamous cell carcinoma.