Depending on the immune milieu of a given HNSCC tumor tissue, the PD-1/PD-L1 axis may be targeted at different levels: The inhibition of PD-1 may prevent binding to PD-L1/PD-L2, while the targeting of PD-L1 may prevent its interaction with PD-1. This evidence concerns the gene PDCD1LG2 and head and neck squamous cell carcinoma.