Likewise, previous studies have shown that both tumor-infiltrating and circulating Tregs upregulate CTLA-4 in HNSCC patients [32,35], being higher the frequency of CTLA-4+ cells on intra-tumoral Tregs as well as their immunosuppressive activity [31] through several mechanisms involving TGF-β1. This evidence concerns the gene TGFB1 and head and neck squamous cell carcinoma.