免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
检查点抑制剂及更多：皮肤恶性肿瘤免疫治疗的系统综述
英文原题：Checkpoint Inhibitors and Beyond: A Systematic Review of Immunotherapy in Cutaneous Malignancies.
查看英文原题
Checkpoint Inhibitors and Beyond: A Systematic Review of Immunotherapy in Cutaneous Malignancies.
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中文摘要
皮肤癌是重要健康问题，亟需更有效治疗方法；免疫检查点抑制剂是近期尤为重要的进展。本研究旨在评估免疫检查点抑制剂、瘤内免疫疗法、靶向药物及其联合方案治疗晚期皮肤恶性肿瘤的疗效和耐受性。按照PRISMA规范系统综述PubMed（2012—2024年），纳入26项研究，包括随机试验、观察性队列、网络荟萃分析和系统综述，评估免疫检查点抑制剂、抗PD-1/PD-L1及抗CTLA-4治疗。结局包括无进展生存期（PFS）、客观缓解率（ORR）、总生存期（OS）、生物标志物及治疗相关不良事件。对涵盖黑色素瘤、基底细胞癌（BCC）、皮肤鳞状细胞癌（cSCC）和Merkel细胞癌（MCC）的26项研究开展荟萃分析，治疗包括PD-1、CTLA-4系统免疫治疗、免疫检查点联合及IL-12电穿孔等新方法。黑色素瘤：PD-1治疗带来持久获益；ipilimumab再治疗后2年生存率为42%。MCC：avelumab治疗OS中位数为12.9个月。cSCC：nivolumab的PFS为8.2个月，cemiplimab的12个月PFS超过53%。靶向治疗：BRAF/MEK抑制剂OS约33个月。新兴策略：TIL疗法和新辅助免疫治疗显示较高病理缓解率和持久应答。
总体而言，联合疗法的生存和应答结局 consistently 优于单药。联合治疗不良事件较常见，30%–59%病例报告重度免疫相关毒性；单药总体更安全。
总之，免疫治疗可带来显著且常持久的获益，但需谨慎选择患者并监测，以平衡疗效与毒性。联合免疫疗法及靶向方案治疗晚期黑色素瘤更有效，但毒性也更高。
展开英文摘要原文
Skin cancers represent a major health concern, and there is a need for more effective treatment approaches, among which immune checkpoint inhibitors have become a particularly important recent development.
This study aimed to explore the efficacy and tolerability of immune checkpoint inhibitors, intratumoral immunotherapies, targeted agents, and their combinations in advanced cutaneous malignancies. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-conform review of PubMed (2012-2024) identified 26 studies, including randomized trials, observational cohorts, network meta-analyses, and systematic reviews, evaluating checkpoint inhibitors, anti-PD-1/PD-L1and anti-CTLA-4. Outcomes included progression-free survival (PFS), objective response rate (ORR), overall survival (OS), biomarkers, and treatment-related adverse events.
This meta-analysis of 26 studies (2012-2024) evaluated treatments for cutaneous malignancies, including melanoma, basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC), covering systemic immunotherapies (PD-1, CTLA-4), combination checkpoint inhibitors, and novel approaches like IL-12 electroporation.
Melanoma: PD-1 therapies showed durable benefits; ipilimumab retreatment yielded 42% two-year survival. MCC: Avelumab achieved a median OS of 12. 9 months. cSCC: Nivolumab PFS 8. 2 months; cemiplimab 12-month PFS >53%. Targeted therapy: BRAF/MEK inhibitors reached OS ~33 months. Emerging strategies: TIL-based and neoadjuvant immunotherapy showed high pathological and durable responses.
Overall, combination therapies consistently outperformed monotherapies in survival and response. Adverse events were common, especially with combination therapy, with severe immune-related toxicities reported in 30-59% of cases, while monotherapies were generally safer.
Overall, immunotherapy offers substantial, often long-lasting benefits, though careful patient selection and monitoring are essential to balance efficacy and toxicity. Combination immunotherapies and targeted regimens are more effective for advanced melanoma, although they have increased toxicity.
论文信息
- 作者
- Rashid Y、Devi S K、Gonzalez-Espinosa TF、Jain J、Dalain M、Baig R、D'Amico GA、Mowo-Wale AG
- 第一作者单位
- Department of Dermatology, Al-Mustansiriyah University, Baghdad, IRQ.
- 通讯作者单位
- Department of Medicine and Surgery, People's University of Medical and Health Sciences for Women, Nawabshah, PAK.
- 文献类型
- 综述
- 期刊
- Cureus2025 Dec
- 原文标识
- PubMed 41527622 · DOI 10.7759/cureus.98959
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