Shi Ruotong, Jia Lin, Lv Zheng, Cui Jiuwei
Oncology Department, Cancer Center, The First Hospital of Jilin University, Changchun, China.
Front Immunol. 2025 Aug 20;16:1632705. doi: 10.3389/fimmu.2025.1632705. eCollection 2025.
Antibody-drug conjugates (ADCs) enhance tumour immunogenicity through multidimensional immune modulation beyond targeted cytotoxicity. The immune remodelling of the tumour microenvironment (TME) suggests potential synergistic mechanisms with immune checkpoint inhibitors (ICIs): ICIs amplify antitumour immune responses by blocking inhibitory signals. Preclinical studies and preliminary clinical evidence demonstrate their synergistic efficacy; however, mechanistic synergy requires further experimental validation. Current challenges encompass the impact of heterogeneous TME on therapeutic outcomes and toxicity risks including interstitial lung disease. Advancing the translational potential of combination therapies necessitates optimised linker designs, development of immunostimulatory payloads, and establishment of precise biomarker frameworks. This review investigates the immunomodulatory mechanisms of ADCs, providing a theoretical foundation and novel directions for antitumour combination therapies and next-generation ADC development.
抗体药物偶联物（ADCs）通过超越靶向细胞毒性的多维免疫调节增强肿瘤免疫原性。肿瘤微环境（TME）的免疫重塑提示了与免疫检查点抑制剂（ICIs）潜在的协同机制：ICIs通过阻断抑制信号放大抗肿瘤免疫反应。临床前研究和初步临床证据证明了它们的协同疗效；然而，机制上的协同作用需要进一步的实验验证。当前的挑战包括异质性TME对治疗结果的影响以及包括间质性肺病在内的毒性风险。提高联合疗法的转化潜力需要优化连接子设计、开发免疫刺激载荷以及建立精确的生物标志物框架。本综述研究了ADCs的免疫调节机制，为抗肿瘤联合疗法和下一代ADC的开发提供了理论基础和新方向。
