Optimizing immunotherapy for head and neck squamous cell carcinoma: recent advances and future directions.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy globally. Despite advancements in surgery, chemotherapy, and radiotherapy, the recurrence rate in advanced-stage HNSCC remains high, with a 5-year overall survival rate of only 35-45%. The significant infiltration of immune cells in HNSCC makes it a prime candidate for immunotherapy. However, response rates for single-agent immunotherapy are below 20%-30%, indicating that many patients do not benefit from monotherapy-based checkpoint blockade treatments. OBJECTIVE: This review aims to explore combined immunotherapy strategies to address the limitations of monotherapy in the treatment of HNSCC. METHODS: We evaluate various combined immunotherapy approaches, including the use of multiple immune checkpoint inhibitors, and their integration with traditional therapies such as chemotherapy, radiotherapy, and surgery. The mechanisms underlying the synergistic effects and the safety profiles of these combination therapies are discussed. CONCLUSION: The integration of immunotherapy with traditional treatment modalities represents a significant advancement in the management of HNSCC. Future research should prioritize the identification of patient populations that are most likely to respond to these combined therapies, as well as the optimization of treatment protocols to enhance clinical outcomes.