Shibata Hirofumi, Kuroki Masashi, Kawaura Ryo, Yamada Tatsuhiko, Iinuma Ryota, Ishihara Hiromasa, Okuda Hiroshi, Mori Kenichi, Ogawa Takenori
Department of Otolaryngology-Head and Neck Surgery, Gifu University Graduate School of Medicine, Gifu, Japan.
Cancer Sci. 2025 Aug 23. doi: 10.1111/cas.70176.
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.
头颈癌（HNCs）是一组异质性恶性肿瘤，包括头颈部鳞状细胞癌（HNSCC）、甲状腺癌和唾液腺癌。尽管采用了多学科治疗方法，但晚期HNCs的治疗效果仍然较差。其中，HNSCC在免疫治疗领域受到了最广泛的研究。免疫检查点抑制剂（ICIs），特别是抗PD-1抗体，已在复发/转移性HNSCC中显示出生存获益，但缓解率仍维持在15%-20%的中等水平，这凸显了需要更有效的治疗策略。最近的进展包括在局部晚期HNSCC中使用新辅助和辅助免疫治疗，这可能会提高病理缓解率和长期生存率。此外，新型免疫治疗方法如肿瘤抗原靶向癌症疫苗和T细胞受体工程化T细胞（TCR-T）疗法正在兴起。这些策略旨在增强肿瘤特异性免疫，特别是在缺乏可靶向驱动突变的肿瘤中。HNSCC中的肿瘤微环境（TME）在调节免疫反应和治疗效果方面起着关键作用。免疫调节剂如HDAC抑制剂、TLR激动剂和VEGF抑制剂已显示出通过改变免疫抑制性TME来增强ICI反应性的前景。此外，识别预测性生物标志物，包括PD-L1表达、肿瘤突变负荷和三级淋巴结构，对于患者选择和反应预测至关重要。本综述全面概述了HNCs免疫治疗的现状和未来方向，特别关注HNSCC。我们强调了当前的临床挑战，并讨论了旨在克服耐药性和改善临床结果的新兴策略。
