Catanzaro Elena, Beltrán-Visiedo Manuel, Galluzzi Lorenzo, Krysko Dmitri V
Cell Death Investigation and Therapy (CDIT) Laboratory, Anatomy and Embryology Unit, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Cancer Research Institute Ghent, Ghent University, Ghent, Belgium.
Cell Mol Immunol. 2025 Jan;22(1):24-39. doi: 10.1038/s41423-024-01245-8. Epub 2024 Dec 10.
While immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the clinical management of various malignancies, a large fraction of patients are refractory to ICIs employed as standalone therapeutics, necessitating the development of combinatorial treatment strategies. Immunogenic cell death (ICD) inducers have attracted considerable interest as combinatorial partners for ICIs, at least in part owing to their ability to initiate a tumor-targeting adaptive immune response. However, compared with either approach alone, combinatorial regimens involving ICD inducers and ICIs have not always shown superior clinical activity. Here, we discuss accumulating evidence on the therapeutic interactions between ICD inducers and immunotherapy with ICIs in oncological settings, identify key factors that may explain discrepancies between preclinical and clinical findings, and propose strategies that address existing challenges to increase the efficacy of these combinations in patients with cancer.
虽然免疫检查点抑制剂（ICI）免疫疗法彻底改变了各种恶性肿瘤的临床治疗方式，但很大一部分患者对作为单一疗法使用的ICI难治，因此需要开发联合治疗策略。免疫原性细胞死亡（ICD）诱导剂作为ICI的联合伙伴引起了相当大的兴趣，至少部分原因是它们能够引发靶向肿瘤的适应性免疫反应。然而，与单独使用任何一种方法相比，涉及ICD诱导剂和ICI的联合方案并不总是显示出卓越的临床活性。在这里，我们讨论了关于ICD诱导剂与ICI免疫疗法在肿瘤学环境中治疗相互作用的越来越多的证据，确定了可能解释临床前和临床研究结果差异的关键因素，并提出了解决现有挑战的策略，以提高这些联合疗法对癌症患者的疗效。
