Unraveling Resistance to Immune Checkpoint Inhibitors in HNSCC: From Mechanisms to Combination Therapies
Year: 2025
Type: preprint
Abstract: Head and neck squamous cell carcinoma (HNSCC), originating from the mucosal epithelium of the oral cavity, pharynx, and larynx, is the most common malignancy of the head and neck region, characterized by high incidence and mortality rates. Due to the complex physiological structure of the head and neck, HNSCC exhibits significant heterogeneity, making the exploration of effective treatment strategies critical for improving patient prognosis. In recent years, immune checkpoint inhibitors (ICIs) targeting programmed death receptor-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have rapidly advanced in the field of oncology. Currently, PD-1 inhibitors pembrolizumab and nivolumab have been approved for first-line and second-line treatment of recurrent/metastatic Head and neck squamous cell carcinoma (R/M HNSCC). However, resistance to immune checkpoint inhibitors is common, with approximately two-thirds of R/M HNSCC cases being unresponsive to immunotherapy. This review comprehensively discusses the types of immunotherapy resistance in HNSCC and the underlying mechanisms contributing to resistance. Furthermore, it reviews current strategies to overcome immunotherapy resistance, providing new perspectives for improving therapeutic efficacy in HNSCC.
Authors: Wenchao Zhao, Qingqing Luo, Bowen Yuan, Huaxin Duan, Siqing Jiang
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4414529082
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