Many immune biomarkers including PD-L1 expression, tumor mutational burden (TMB), tumor immune cell infiltration, circulating immune cells, HPV, changes within the microbiome, and certain risk factors such as smoking have been suggested as predictors of HNSCC response to ICI, but the data remain in its infancy, without causative association and often with conflicting results within the literature [9]. This evidence concerns the gene CD274 and head and neck squamous cell carcinoma.