帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好,仅出现轻度胃肠道不良事件,并展现出有前景的活性,值得在随机试验中进一步研究。
英文原题:Head and Neck Cancer Immunotherapy: Overcoming Limitations and Enhancing Efficacy.
免疫检查点抑制剂(ICIs),尤其是抗 PD-1 抗体,已在 R/M HNSCC 中显示出生存获益,但缓解率仍不理想,仅为 15%-20%,凸显出需要更有效的策略。
头颈部癌症(HNC)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。尽管采用多学科治疗,晚期 HNC 结局仍较差。其中,HNSCC 是免疫治疗领域研究最充分的类型。免疫检查点抑制剂(ICI),尤其是抗 PD-1 抗体,已改善复发/转移性(R/M)HNSCC 患者生存,但应答率仍仅为 15%–20%,凸显开发更有效策略的必要性。近期进展包括局部晚期 HNSCC 的新辅助和辅助免疫治疗,可能提高病理缓解率和长期生存。此外,肿瘤抗原靶向癌症疫苗和 TCR 工程化 T 细胞(TCR-T)等新型免疫治疗方法正在兴起,旨在增强肿瘤特异性免疫,特别适用于缺乏可靶向驱动突变的肿瘤。HNSCC 肿瘤微环境(TME)在调节免疫应答和治疗效力方面发挥关键作用。HDAC 抑制剂、TLR 激动剂和 VEGF 抑制剂等免疫调节药物通过改变免疫抑制性 TME,有望增强 ICI 应答。此外,PD-L1 表达、肿瘤突变负荷和三级淋巴结构等预测性生物标志物对患者筛选及应答预测至关重要。本综述全面概述 HNC 免疫治疗现状和未来方向,重点关注 HNSCC;作者强调持续存在的临床挑战,并讨论旨在克服耐药、改善临床结局的新兴策略。
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.
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