CTLA4 and neoplasm: The mechanisms include: (1) immune cell dysfunction within the tumor microenvironment (TME) and in the peripheral blood of patients with HNSCC [39]; (2) defects in antigen presenting of tumor cells [40]; (3) secretion of cytokines in the TME in favor of immunosuppression (e.g., TGF-beta) [41]; (4) presence of tumor immunosuppressive cells (e.g., T regulatory cells, tumor associated macrophages, and myeloid derived suppressor cells) [42]; and (5) upregulation of immune checkpoints, including PD-L1 and CTLA-4 [43].