Mechanisms of Resistance and Therapeutic Perspectives in Immunotherapy for Advanced Head and Neck Cancers.

Simple Summary: The programmed death-1 receptor monoclonal antibody treatments pembrolizumab and nivolumab have been successful in the treatment of recurrent or metastatic head and neck cancer. However, about 60% of patients will experience recurrence after this immunotherapeutic treatment. This is believed to be due to a combination of innate and adaptive tumor characteristics that suppress the body's immune response to recurrent or metastatic head and neck cancer. This review details the mechanisms of these innate and adaptive characteristics and describes potential treatments that could be used to target and overcome these immunotherapy resistance mechanisms. These include the combinations of novel and existing therapies aimed to overcome current challenges with immunotherapy resistance and hopefully leading to improved patient outcomes. Immunotherapy is emerging as an effective treatment for advanced head and neck cancers and interest in this treatment modality has led to rapid expansion of this research. Pembrolizumab and nivolumab, monoclonal antibodies directed against the programmed cell death-1 (PD-1) receptor, are US Food and Drug Administration (FDA)- and European Medical Agency (EMA)-approved immunotherapies for head and neck squamous cell carcinoma (HNSCC). Resistance to immunotherapy is common, with about 60% of patients with recurrent or metastatic HNSCC not responding to immunotherapy and only 20–30% of patients without disease progression in the long term. Overcoming resistance to immunotherapy is therefore essential for augmenting the effectiveness of immunotherapy in HNSCC. This review details the innate and adaptive mechanisms by which head and neck cancers can become resistant to immunotherapeutic agents, biomarkers that can be used for immunotherapy patient selection, as well as other factors of the tumor microenvironment correlated with therapeutic response and prognosis. Numerous combinations and novel immunotherapies are currently being trialed, based on better understood immune evasion mechanisms. These potential treatments hold the promise of overcoming resistance to immunotherapy in head and neck cancers. [ABSTRACT FROM AUTHOR]