Figure 2.

Potential immunotherapeutic strategies to treat metastatic/recurrent HNSCC. Suggested possible strategies to improve the immune response of these patients. In HPV and/or EBV-positive HNSCC tumors, new approaches targeting immunogenic viral antigens, as therapeutic vaccines as well as expansion of existing viral antigen-specific T cells (e.g., anti-LMP specific T cells) for adoptive transfer in combination with immune checkpoint inhibitors blockade (anti-PD-1/PD-L-1 or anti-CTLA-4). HNSCC is associated with somatic mutations and therefore whole genome sequencing would allow prediction of mutated peptides and development of patients-personalized vaccines that can be used in combination with standard chemo/radiotherapy protocols. Specific tumor-associated neoantigens such as NY-ESO-1 and PD-L1 can also be used as immunotherapeutic targets. Clinical protocols should be developed to expand existing anti-NY-ESO1 or anti-PD-L1-specific T cells for adoptive transfer in combination with other immune checkpoint inhibitors blockade. HNSCC, head and neck squamous cell carcinoma; HPV, human papilloma virus; EBV, Epstein-Barr virus; LMP, latent membrane protein; EBNA, EBV-induced nuclear antigen; PD-1, programmed cell death protein 1; PD-L1, programmed cell death protein 1 ligand; PBMCs, peripheral blood mononuclear cells; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; NY-ESO-1, New York esophageal squamous cell carcinoma 1; IL 4/7, interleukins 4 and 7; CTL, cytotoxic T lymphocytes.