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创新免疫治疗方法:利用肿瘤学中双重检查点阻断的协同作用

英文原题:Innovative immunotherapy approaches: harnessing synergy of dual checkpoint blockade in oncology.

PubMed 2026/01/24(内容时间) Naunyn Schmiedebergs Arch Pharmacol Q2 · IF 4(JCR 2025)

研究概要

本综述全面评估了用于癌症免疫治疗的协同免疫检查点抑制剂(ICI)策略及其不断演变的联合方案,重点介绍了双重及策略性设计的治疗选择。

中文摘要

本综述对用于癌症免疫治疗的协同免疫检查点抑制剂(ICI)策略及其不断演变的联合方案进行了全面评估,重点介绍了双重及策略性设计的治疗选择。它强调了对检查点阻断、肿瘤微环境(TME)以及创新性抑制性和刺激性靶点的重要见解,包括CTLA-4、PD-1/PD-L1、LAG-3、TIM-3和TIGIT。它讨论了临床前和临床数据,证明化疗、放疗、靶向药物和过继性细胞转移等联合治疗如何能够增强治疗反应并规避耐药性。本综述系统性地概述了重要的临床研究和监管批准,重点介绍了在黑色素瘤、非小细胞肺癌、肾细胞癌和结直肠癌中改善的结果。对生物标志物开发、序贯和时机优化以及免疫相关不良事件的管理进行了全面评估,同时结合了AI驱动的生物标志物识别等新方法以及肠道微生物组对免疫检查点抑制剂疗效的影响。研究表明,提高癌症免疫治疗疗效和精准度的最佳方法是通过实施合理的联合策略,针对多种免疫逃逸机制并纳入对肿瘤微环境的调控。这将改善所有癌症类型的长期生存和临床结局。

展开英文摘要原文

This review offers a comprehensive assessment of synergistic immune checkpoint inhibitor (ICI) strategies and their evolving combinations for cancer immunotherapy, highlighting dual and strategically designed treatment options. It emphasizes essential insights into checkpoint blockade, the tumor microenvironment (TME), and innovative inhibitory and stimulatory targets, including CTLA-4, PD-1/PD-L1, LAG-3, TIM-3, and TIGIT. It discusses preclinical and clinical data demonstrating how combination therapies, such as chemotherapy, radiation, targeted medications, and adoptive cell transfer, can enhance therapeutic responses and circumvent drug resistance. The review systematically outlines important clinical research and regulatory approvals, highlighting improved results in melanoma, non-small cell lung cancer, renal cell carcinoma, and colorectal cancer. A comprehensive assessment of biomarker development, sequencing and timing optimization, and the management of immune-related adverse events is undertaken, in conjunction with novel methodologies such as AI-driven biomarker identification and the impact of the gut microbiome on the efficacy of immune checkpoint inhibitors. The research indicates that the optimal approach to enhance treatment efficacy and precision in cancer immunotherapy is through the implementation of rational combination strategies that address multiple immune evasion mechanisms and incorporate manipulation of the tumor microenvironment. This will improve long-term survival and clinical outcomes across all cancer types.

论文信息

作者
Shaik R、Varikuppala M、Badampudi S、Jabeen A、Hamzah MA、Zehra FU、Unnisa A、Mohammed JS
单位
Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India. shaikrahaman_sch@jamiahamdard.ac.in.India
文献类型
综述
期刊
Naunyn-Schmiedeberg's archives of pharmacology2026 Apr
原文标识
PubMed 41579169 · DOI 10.1007/s00210-025-04884-4