Immunotherapy is emerging as an effective treatment for advanced head and neck cancers and interest in this treatment modality has led to rapid expansion of this research. Pembrolizumab and nivolumab, monoclonal antibodies directed against the programmed cell death-1 (PD-1) receptor, are US Food and Drug Administration (FDA)- and European Medical Agency (EMA)-approved immunotherapies for head and neck squamous cell carcinoma (HNSCC). Resistance to immunotherapy is common, with about 60% of patients with recurrent or metastatic HNSCC not responding to immunotherapy and only 20–30% of patients without disease progression in the long term. Overcoming resistance to immunotherapy is therefore essential for augmenting the effectiveness of immunotherapy in HNSCC. This review details the innate and adaptive mechanisms by which head and neck cancers can become resistant to immunotherapeutic agents, biomarkers that can be used for immunotherapy patient selection, as well as other factors of the tumor microenvironment correlated with therapeutic response and prognosis. Numerous combinations and novel immunotherapies are currently being trialed, based on better understood immune evasion mechanisms. These potential treatments hold the promise of overcoming resistance to immunotherapy in head and neck cancers.
免疫疗法正逐渐成为晚期头颈部癌症的有效治疗手段，对该治疗模式的关注推动了相关研究的快速发展。针对程序性细胞死亡蛋白-1（PD-1）受体的单克隆抗体帕博利珠单抗和纳武利尤单抗，已获得美国食品药品监督管理局（FDA）及欧洲药品管理局（EMA）批准用于头颈部鳞状细胞癌（HNSCC）的免疫治疗。免疫治疗耐药现象较为普遍，约60%的复发或转移性头颈部鳞癌患者对免疫治疗无应答，仅20-30%的患者能实现长期无疾病进展。因此，克服免疫治疗耐药对于提升头颈部鳞癌免疫治疗效果至关重要。本综述详细阐述了头颈部癌症对免疫治疗药物产生耐药性的先天与适应性机制、可用于免疫治疗患者筛选的生物标志物，以及与治疗反应和预后相关的肿瘤微环境其他因素。基于对免疫逃逸机制更深入的理解，目前正在开展多种联合疗法及新型免疫疗法的临床试验。这些潜在治疗方法有望克服头颈部癌症对免疫治疗的耐药问题。
肿瘤(癌症)患者之家