It is noteworthy that the introduction of immune checkpoint inhibitors (ICI) has reshaped the treatment landscape of HNSCC.701–704 Inhibition of CDK4/6 has been shown to trigger immune responses, particularly by increasing antigen presentation in tumor cells and depleting the regulatory T cell (Treg) repertoire.681,682 Building on this knowledge, a recent phase I study evaluated the combination of palbociclib, cetuximab, and avelumab in advanced HNSCC, demonstrating that this triplet treatment is safe and exhibits promising antitumor activity (ORR 42%).705. This evidence concerns the gene CDK4 and head and neck squamous cell carcinoma.