Enhancement of Immunotherapies in Head and Neck Cancers Using Biomaterial-Based Treatment Strategies

Head and neck squamous cell carcinoma (HNSCC) is a challenging disease to treat because of typically late-stage diagnoses and tumor formation in difficult-to-treat areas, sensitive to aggressive or invasive treatments. To date, HNSCC treatments have been limited to surgery, radiotherapy, and chemotherapy, which may have significant morbidity and often lead to long-lasting side effects. The development of immunotherapies has revolutionized cancer treatment by providing a promising alternative to standard-of-care therapies. However, single-agent immunotherapy has been only modestly effective in the treatment of various cancers, including HNSCC, with most patients receiving no overall benefit or increased survival. In addition, single-agent immunotherapy's limitations, namely immune-related side effects and the necessity of multidose treatments, must be addressed to further improve treatment efficacy. Biocompatible biomaterials, in combination with cancer immunotherapies, offer numerous advantages in the concentration, localization, and controlled release of drugs, cancer antigens, and immune cells. Biomaterial structures are diverse, and their design can generally be customized to enhance immunotherapy response. In preclinical settings, the use of biomaterials has shown great promise in improving the efficacy of single-agent immunotherapy. Herein, we provide an overview of current immunotherapy treatments for HNSCC and their limitations, as well as the potential applications of biomaterials in enhancing cancer immunotherapies. Impact StatementAdvances in anticancer immunotherapies for the past 30 years have yielded exciting clinical results and provided alternatives to long-standing standard-of-care treatments, which are associated with significant toxicities and long-term morbidity. However, patients with head and neck squamous cell carcinoma (HNSCC) have not benefited from immunotherapies as much as patients with other cancers. Immunotherapy limitations include systemic side effects, therapeutic resistance, poor delivery kinetics, and limited patient responses. Biomaterial-enhanced immunotherapies, as explored in this review, are a potentially powerful means of achieving localized drug delivery, sustained and controlled drug release, and immunomodulation. They may overcome current treatment limitations and improve patient outcomes and care.