肿瘤细胞治疗研究
英文原题：Advances and challenges in immunotherapy in head and neck cancer.
Advances and challenges in immunotherapy in head and neck cancer.
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头颈部鳞状细胞癌（HNSCC）尽管在手术、放疗和化疗方面取得了进展，但仍是一种具有挑战性的恶性肿瘤，生存结局不尽如人意。
头颈部鳞状细胞癌（HNSCC）尽管在手术、放疗和化疗方面取得了进展，但仍是预后欠佳的难治性恶性肿瘤。免疫治疗，特别是靶向程序性细胞死亡蛋白1（PD-1）/程序性细胞死亡配体1（PD-L1）的免疫检查点抑制剂（ICIs），已改变了治疗模式，但其在HNSCC中的全部潜力仍在探索中。本综述评估了免疫治疗在局部晚期（LA）和复发/转移性（R/M）HNSCC中的当前格局，讨论了关键临床试验、新兴生物标志物和新型治疗策略。对于LA HNSCC，III期试验如KEYNOTE-412和JAVELIN Head and Neck 100未能在未选择人群中证明ICI联合放化疗的生存获益，尽管事后分析提示在PD-L1阳性肿瘤中具有疗效。近期研究，包括KEYNOTE-689和NIVOPOSTOP GORTEC 2018-01，表明围手术期ICIs在可切除疾病中具有潜在获益。在R/M HNSCC中，ICIs已重新定义了标准治疗。KEYNOTE-040和CheckMate 141促使美国食品药品监督管理局（FDA）批准帕博利珠单抗和纳武利尤单抗，而KEYNOTE-048确立了帕博利珠单抗单药用于PD-L1联合阳性评分（CPS）≥1的患者，以及帕博利珠单抗联合化疗作为一线治疗。然而，双重检查点阻断试验（KESTREL、CheckMate 651）结果不一，凸显了免疫抵抗的复杂性。除ICIs外，新兴策略包括溶瘤病毒疗法、CAR-T 细胞疗法（CAR-T）和癌症疫苗，在临床前和早期临床阶段显示出令人鼓舞的结果。PD-L1表达、肿瘤突变负荷（TMB）和人乳头瘤病毒（HPV）状态等生物标志物在治疗选择中发挥关键作用，但需进一步验证。尽管取得进展，挑战依然存在，包括异质性缓解率、免疫相关毒性以及免疫治疗在多模式治疗方案中的最佳整合。未来研究应聚焦于优化基于生物标志物的治疗算法、开发合理的免疫治疗联合方案，并利用肿瘤微环境修饰以增强疗效。
Head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy with suboptimal survival outcomes despite advances in surgery, radiotherapy, and chemotherapy. Immunotherapy, particularly immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1), has transformed treatment paradigms, yet its full potential in HNSCC is still being explored. This review evaluates the current landscape of immunotherapy in both locally advanced (LA) and recurrent/metastatic (R/M) HNSCC, discussing key clinical trials, emerging biomarkers, and novel therapeutic strategies. For LA HNSCC, phase III trials such as KEYNOTE-412 and JAVELIN Head and Neck 100 failed to demonstrate survival benefits with ICI-chemoradiotherapy combinations in unselected populations, though post hoc analyses suggest efficacy in PD-L1-positive tumors. Recent studies, including KEYNOTE-689 and NIVOPOSTOP GORTEC 2018-01, indicate potential benefits of perioperative ICIs in resectable disease. In R/M HNSCC, ICIs have redefined the standard of care. KEYNOTE-040 and CheckMate 141 led to Food and Drug Administration (FDA) approvals of pembrolizumab and nivolumab, while KEYNOTE-048 established pembrolizumab monotherapy for PD-L1 combined positive score (CPS) 1 and pembrolizumab plus chemotherapy as first-line treatment. However, dual checkpoint blockade trials (KESTREL, CheckMate 651) have yielded mixed results, highlighting the complexity of immune resistance. Beyond ICIs, emerging strategies include oncolytic virotherapy, chimeric antigen receptor-T cell therapy (CAR-T), and cancer vaccines, with promising preclinical and early-phase clinical results. Biomarkers such as PD-L1 expression, tumor mutational burden (TMB), and Human Papillomavirus (HPV) status play a critical role in treatment selection, but further validation is needed. Despite advancements, challenges persist, including heterogeneous response rates, immune-related toxicities, and optimal integration of immunotherapy in multimodal treatment regimens. Future research should focus on refining biomarker-driven treatment algorithms, developing rational immunotherapy combinations, and leveraging tumor microenvironment modifications to enhance therapeutic efficacy.
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