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Head and Neck Cancer Immunotherapy: Overcoming Limitations and Enhancing Efficacy
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Head and Neck Cancer Immunotherapy: Overcoming Limitations and Enhancing Efficacy
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Journal Article
Head and Neck Cancer Immunotherapy: Overcoming Limitations and Enhancing Efficacy
2025
Overview
Head and neck cancers (HNCs) are a heterogeneous group of malignancies, including head and neck squamous cell carcinoma (HNSCC), thyroid carcinoma, and salivary gland carcinoma. Despite multidisciplinary treatment approaches, outcomes for advanced HNCs remain poor. Among these, HNSCC has been the most extensively studied in the field of immunotherapy. Immune checkpoint inhibitors (ICIs), particularly anti‐PD‐1 antibodies, have demonstrated survival benefits in R/M HNSCC, but response rates remain modest at 15%–20%, highlighting the need for more effective strategies. Recent advances include the use of neoadjuvant and adjuvant immunotherapy in locally advanced HNSCC, which may improve pathological response rates and long‐term survival. Additionally, novel immunotherapeutic approaches such as tumor antigen‐targeted cancer vaccines and T‐cell receptor‐engineered T‐cell (TCR‐T) therapy are emerging. These strategies aim to enhance tumor‐specific immunity, especially in tumors lacking targetable driver mutations. The tumor microenvironment (TME) in HNSCC plays a pivotal role in modulating immune response and therapeutic efficacy. Immunomodulatory agents such as HDAC inhibitors, TLR agonists, and VEGF inhibitors have shown promise in enhancing ICI responsiveness by altering the immunosuppressive TME. Moreover, the identification of predictive biomarkers, including PD‐L1 expression, tumor mutational burden, and tertiary lymphoid structures, is crucial for patient selection and response prediction. This review provides a comprehensive overview of the current landscape and future directions of immunotherapy for HNCs, with a particular focus on HNSCC. We highlight ongoing clinical challenges and discuss emerging strategies aimed at overcoming resistance and improving clinical outcomes. ICI‐included therapies are standard for R/M HNSCC patients. In particular, neoadjuvant ICI therapy shows promising clinical results even in nontreated resectable HNSCC patients. In addition, cancer vaccine, immune cell‐based therapy, immunomodulation therapy, and TME targeting therapy may combine with ICI.
Publisher
John Wiley & Sons, Inc,Wiley
Subject
/ Cancer Vaccines - immunology
/ Cancer Vaccines - therapeutic use
/ Genes
/ Head and Neck Neoplasms - immunology
/ Head and Neck Neoplasms - pathology
/ Head and Neck Neoplasms - therapy
/ Humans
/ Immune checkpoint inhibitors
/ Immune Checkpoint Inhibitors - pharmacology
/ Immune Checkpoint Inhibitors - therapeutic use
/ Kinases
/ Mutation
/ Review
/ Squamous Cell Carcinoma of Head and Neck - immunology
/ Squamous Cell Carcinoma of Head and Neck - therapy
/ Tumor Microenvironment - drug effects
/ Tumor Microenvironment - immunology
/ Tumors
