Although a new treatment paradigm has been established placing pembrolizumab + platinum and infusional fluorouracil as the new standard as the first line for R/M HNSCC, ~64% of patients will not benefit from the significant tumor regression criteria, indicating innate, adaptive resistance to the blockade of PD-1/PD-L1 ligation. Here, CD274 is linked to head and neck squamous cell carcinoma.