Current status and perspective of immunotherapy for head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC), has still a high mortality rate even if several multimodal treatments have been developed in the advanced stages.

In recent years, immunotherapy was introduced for the treatment of advanced and metastatic HNSCC with favorable effects on survival and quality of life. Currently, pembrolizumab plus or less chemotherapy is recommended in patients with CPS > 1 in metastatic HNSCC, while nivolumab is used in the second line setting for platinum-refractory disease. However, despite the benefits of these agents, most patients progress after immunotherapy. New approaches to overcome HNSCC immune escape are ongoing, involving antibodies against other immunological locks such as LAG-3, TIGIT, TIM-3, and CD134 (OX40). Moreover, T-lymphocyte activators like GITR and vaccine strategies based on peptides, DNA and RNA against HPV-positive HNSCCs, tumor-associated antigens, dendritic cells, and personalized cancer vaccines have been recently developed.

Future research is crucial to determine the optimal setting for treatment with immunological checkpoint inhibitors through the use of new prognostic biomarkers. This review discusses both completed and ongoing clinical trials with PD-1/PDL-1 and new checkpoint inhibitors and immunotherapies. It also addresses mechanisms of resistance to immunotherapy, potential therapeutic strategies to overcome this resistance, biomarkers and side effects.