Head and neck squamous cell carcinoma (HNSCC) represents the seventh leading malignancy worldwide with a low 5-year survival rate and poor prognosis.1 Despite a variety of progresses in combined modality treatments over the past three decades, the overall survival rate is less than 50% in 5 years for HNSCC patients.2 Targeted therapy and immunotherapy have emerged as the promising strategies in cancer therapy,3 however, immune checkpoint inhibitors such as anti-PD-1/PDL1 therapy demonstrated limited responses in HNSCC patients.4 The gene discussed is CD274; the disease is cancer.