Combining immunotherapy and radiotherapy in head and neck squamous cell cancers: which perspectives?

Abstract

The role of the immune system is important in both initiation and development of head and neck cancers. Various immune checkpoints have been discovered that can be exploited by cancer to evade immune mediated destruction. Therefore, immune checkpoint inhibitors have been developed to overcome cancer immune-evasion and are currently in clinical use in head and neck cancers. In addition, the immune system appears to play an important role in the response to radiotherapy. The combination of immunotherapy with radiotherapy may increase the ability to induce immunogenic death by removing the locks blocking the immune system. Although the antitumour efficacy of radiotherapy is based primarily on the toxicity of DNA damage, studies have suggested that this efficacy is based not only on this local cytotoxic and antiproliferative effect, but also on the interactions between the tumor and its microenvironment that are altered. Thus, the cytotoxic action of radiotherapy on tumor cells provides T lymphocytes with tumor neoantigens, and releases proinflammatory cytokines that promote the immune response. Cell death inducing this type of immune response is called immunogenic death. Therefore, several phase 3 clinical trials are currently ongoing evaluating the combination of radiotherapy and immune checkpoint inhibitors in head and neck cancers. Combining immunotherapy and radiotherapy in head and neck cancers is promising. Several phase 3 clinical trials are ongoing that may be practice changing.