肿瘤细胞治疗研究
英文原题：Advances in Immunotherapy for Head and Neck Squamous Cell Carcinoma: Focus on PD-1/PD-L1 Blockade and Beyond.
Advances in Immunotherapy for Head and Neck Squamous Cell Carcinoma: Focus on PD-1/PD-L1 Blockade and Beyond.
头颈部鳞状细胞癌（HNSCC）是全球第七大常见癌症，其病因亚型——致癌物驱动型（人乳头瘤病毒[HPV]阴性）和HPV驱动型——塑造了肿瘤的免疫原性和治疗反应。
头颈部鳞状细胞癌（HNSCC）是全球第七大常见癌症，其病因亚型——致癌物驱动型（人乳头瘤病毒[HPV]阴性）和HPV驱动型——塑造了肿瘤的免疫原性和治疗反应。本综述重点阐述免疫治疗的演变，聚焦于PD-1/PD-L1阻断。HPV阳性肿瘤具有“热”微环境，特征为密集的TIL（肿瘤浸润淋巴细胞）（TILs）和PD-L1上调，从而获得更好的免疫检查点抑制剂（ICI）疗效。相比之下，HPV阴性病例则呈现“冷”的免疫抑制特征，ICI反应较差。KEYNOTE-048和CheckMate 141等里程碑式试验确立了帕博利珠单抗和纳武利尤单抗作为复发/转移性HNSCC的标准治疗，相较于EXTREME方案（西妥昔单抗联合铂类化疗），中位OS（总生存期）提高了2至4个月，尤其是在PD-L1联合阳性评分（CPS）⩾ 1的患者中。联合策略通过多种机制增强疗效：化疗诱导免疫原性细胞死亡，放疗引发远隔效应，西妥昔单抗提供额外的抗肿瘤活性。在局部晚期疾病中，KEYNOTE-689试验证明围手术期帕博利珠单抗相较于安慰剂具有更优的无事件生存期（59.7 vs 29.6个月），支持治疗降阶梯策略。免疫相关不良事件的管理遵循已建立的NCCN/SITC指南。新兴疗法，包括抗LAG-3/TIM-3和溶瘤病毒，针对耐药机制。未来努力强调多组学生物标志物和公平可及性，以优化这种异质性恶性肿瘤的结局。
Head and neck squamous cell carcinoma (HNSCC) ranks as the seventh most common cancer globally, with etiological subtypes-carcinogen-driven (human papillomavirus [HPV-negative]) and HPV-driven-shaping tumor immunogenicity and treatment responses. This review highlights immunotherapy's evolution, focusing on PD-1/PD-L1 blockade. HPV-positive tumors feature a "hot" microenvironment with dense tumor-infiltrating lymphocytes (TILs) and PD-L1 upregulation, yielding better immune checkpoint inhibitor (ICI) outcomes. In contrast, HPV-negative cases exhibit a "cold," immunosuppressive profile with inferior ICI responses. Landmark trials like KEYNOTE-048 and CheckMate 141 established pembrolizumab and nivolumab as standards for recurrent/metastatic HNSCC, improving median OS (overall survival) by 2 to 4 months over the EXTREME regimen (cetuximab plus platinum-based chemotherapy), especially in patients with PD-L1 Combined Positive Score (CPS) ⩾ 1. Combination strategies enhance efficacy through multiple mechanisms: chemotherapy induces immunogenic cell death, radiotherapy elicits abscopal effects, and cetuximab provides additional antitumor activity. In locally advanced disease, the KEYNOTE-689 trial demonstrated superior event-free survival with perioperative pembrolizumab versus placebo (59.7 vs 29.6 months), supporting treatment de-escalation strategies. Management of immune-related adverse events follows established NCCN/SITC guidelines. Emerging therapies, including anti-LAG-3/TIM-3 and oncolytic viruses, target resistance. Future efforts emphasize multiomic biomarkers and equitable access to optimize outcomes in this heterogeneous malignancy.
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