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.
肿瘤细胞治疗研究
英文原题:Expanding indications of immune checkpoint inhibitors: a decade of success going strong.
Expanding indications of immune checkpoint inhibitors: a decade of success going strong.
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自 2011 年以来,ICIs 几乎渗透到肿瘤学的所有领域,对多种癌症类型产生了有意义的影响。除了扩大适应症外,它们还为许多应答者提供了持久获益的潜力。在黑色素瘤、头颈部、肾脏、肝脏和尿路上皮癌中,临床试验之外的 PD-L1 检测已不再需要。PD-1 ± CTLA-4 抑制在微卫星不稳定性高癌症中的肿瘤不可知疗效已得到充分确立。在其他癌症亚群中获益有限,这凸显了生物标志物发现和治疗策略优化的必要性,包括在 ICIs 基础上加用抗体-药物偶联物、下一代检查点调节、个性化新抗原疫苗以及工程化细胞免疫治疗。有效的未来疗法还应解决肿瘤细胞的全面分析、其分子表达模式以及肿瘤微环境不断变化的动态。
免疫检查点抑制剂(ICIs)通过靶向细胞毒性T淋巴细胞相关蛋白4(CTLA-4)和程序性细胞死亡蛋白1/程序性死亡配体1(PD-1/PD-L1),彻底改变了肿瘤学格局,从而使多种恶性肿瘤产生治疗应答。尽管取得了这些进展,但在许多癌症中获益仍然有限。涵盖领域:通过PubMed、Embase和Cochrane Library进行了叙述性文献综述,以识别2000年1月1日至2025年12月31日期间的英文出版物。符合条件的来源包括关键性试验、真实世界研究、综述以及相关临床实践指南。
INTRODUCTION: Immune checkpoint inhibitors (ICIs) have transformed oncology by targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1), thereby enabling responses across multiple malignancies. Despite these advances, benefits remain limited in many cancers. AREAS COVERED: A narrative literature review was conducted using PubMed, Embase, and the Cochrane Library to identify English-language publications from 1 January 2000, through 31 December 2025. Eligible sources included pivotal trials, real-world studies, reviews, and relevant clinical practice guidelines. EXPERT OPINION: Since 2011, ICIs have permeated virtually all fields of oncology, with meaningful impact across many cancer types.
Beyond expanding indications, they offer potential for durable benefit in many responders. In melanoma, head and neck, kidney, liver, and urothelial cancers, PD-L1 testing outside clinical trials is no longer required. Tumor-agnostic efficacy of PD-1 ± CTLA-4 inhibition in microsatellite instability-high cancers is well established.
Limited benefit in other cancer subsets highlights the need for biomarker discovery and optimization of therapeutic strategies, including addition of antibody-drug conjugates to ICIs, next-generation checkpoint modulation, personalized neoantigen vaccines, and engineered cellular immunotherapy. Effective future therapies should also address comprehensive profiling of tumor cells, their molecular expression patterns, and constantly changing dynamics of the tumor microenvironment.
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