Biomarkers that have shown potential to determine improved clinical response in HNSCC include the tumor mutational burden, CCND1 amplification (CCND1 encodes cyclin D1, which regulates the retinoblastoma protein activity and cell-cycle progression), PD-1, IFN-γ, tumor-infiltrating lymphocytes (TILs) and cancer-associated fibroblasts (CAFs), CTLA-4, exosomes, CXCL, MTAP and SFR4/CPXM1/COL5A1 molecules [25,59,60,61,62,63,64,65,66,67,68,69]. Here, CTLA4 is linked to head and neck squamous cell carcinoma.