In HNSCC, CTLA-4 competes with CD28 to bind to the B7 family of molecules on APCs, inducing T cell dysfunction after binding to the B7 protein, thereby leading to immunosuppression.[73,74] CTLA-4 can also prevent T cells from being further activated by binding to 2 ligands on the surface of APC, CD80 and CD86, and transmitting negative signals.[75] Also, CTLA-4 combines with PI3K, resulting in phosphorylation of AKT, which is more likely to cause inactivation of pro-apoptotic factor BAD, and upregulation of anti-apoptotic factors Bcl-xL and Bcl-2, thus boosting tumor immune tolerance.[76]. This evidence concerns the gene CTLA4 and head and neck squamous cell carcinoma.