Immunotherapy in head and neck cancer: evidence and perspectives

Head and neck squamous cell carcinomas evade immune response through multiple immunologic resistance mechanisms. Two of the most commonly involved checkpoint inhibitory mechanisms are CTLA-4 and PD-1/PD-L1, which act at earlier and later stages of immune response to tumors. Pembrolizumab and nivolumab are PD-1 antibodies that interrupt the immunosuppressive pathway of inhibitory checkpoints, which are used by tumor cells to prevent immune reaction. Both recently gained US FDA approval for the treatment of patients with recurrent or metastatic head and neck cancer with disease progression during or following platinum containing chemotherapy. No conclusions can be drawn on the role of PD-L1 in identifying patients responding to immunotherapy, given that similar studies lead to contrasting results. It will be crucial to identify predictive markers of immunotherapy response, and to evaluate them prospectively. A better understanding of the complex network between tumor, immune system and other oncologic treatments will help us to develop more efficient multimodality treatments.