Recently, primary resistance to PD-1/PD-L1-targeted immune checkpoint immunotherapy that is observed in more than 80% of HNSCC patients in the R/M setting (12, 13) has been related to intratumoral hypoxia as shown by an inverse spatial distribution of hypoxia- and immune-response markers in HNSCC specimen (10). The gene discussed is CD274; the disease is head and neck squamous cell carcinoma.