As use of PD-L1 expression as biomarker is only able to enrich responders among treated patients, clinical characteristics such as T and N category still play the most important role in treatment decision for curative HNSCC (42–47), as (compared to other solid tumors) reliable biomarkers like micro-satellite instability (e.g. MSI) for treatment stratification are very infrequent or even missing; ex-vivo testing and monitoring of in vivo responses via liquid biopsies, however, may overcome the dilemma of missing biomarkers. The gene discussed is CD274; the disease is head and neck squamous cell carcinoma.