Insights from investigations into mechanisms of immunotherapy treatment failure have led to the advent of tumor mutational burden (TMB) and microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) as putative biomarkers of PD-1 checkpoint inhibitor response in HPV-negative HNSCC, in addition to the already well-established role of PD-1 expression as a biomarker for PD-1 inhibitor response [79]. Here, PDCD1 is linked to head and neck squamous cell carcinoma.