Department of Bioengineering, Rice University, Houston, Texas, USA.
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Kaohsiung J Med Sci. 2021 Jun;37(6):448-458. doi: 10.1002/kjm2.12375. Epub 2021 Feb 26.
Immunogenic cell death (ICD) refers to a form of regulated cell death that activates adaptive immunity, forming long-term immunological memory. Using chemotherapeutic drugs to induce ICD in cancer cells can help create an inflamed, immunogenic tumor environment, key for optimal immune checkpoint blockade (ICB) therapy response. ICB targets immune checkpoints such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed death 1 (PD-1). Durable responses and better quality of life in ICB patients compared with many other treatments has prompted additional investigation into its therapeutic potential and possible approaches, in an effort to further understand the functions of the costimulatory molecules and how new treatments may be designed. In this review, we will summarize ICD induction, including stress responses, damage-associated molecular patterns, and various assays by which immunogenicity is evaluated in dying cells. In addition, the mechanisms and biomarkers underlying the CTLA4 and PD-1 pathways of checkpoint blockade will be covered. Finally, we will review the synergistic effects of ICD induction combined with ICB therapy, as well as combination blockade therapies involving the use of multiple drugs.
免疫原性细胞死亡（ICD）是一种受调控的细胞死亡形式，可激活适应性免疫，形成长期的免疫记忆。使用化疗药物诱导癌细胞发生 ICD 有助于产生炎症、免疫原性的肿瘤微环境，这是优化免疫检查点阻断（ICB）治疗反应的关键。ICB 靶向免疫检查点，如细胞毒性 T 淋巴细胞相关抗原 4（CTLA4）和程序性死亡受体 1（PD-1）。与许多其他治疗方法相比，ICB 患者具有持久的反应和更好的生活质量，这促使人们进一步研究其治疗潜力和可能的方法，以努力进一步了解共刺激分子的功能以及如何设计新的治疗方法。在这篇综述中，我们将总结 ICD 的诱导，包括应激反应、损伤相关分子模式以及评估死亡细胞免疫原性的各种检测方法。此外，还将介绍 CTLA4 和 PD-1 通路检查点阻断的机制和生物标志物。最后，我们将综述 ICD 诱导与 ICB 治疗联合应用的协同作用，以及涉及多种药物联合阻断治疗的方法。
