Sen Sajal, Karoscik Krystle, Maier Esther, Arambula Jonathan F
Department of Biological Engineering, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA.
InnovoTEX, Inc. 3800 N. Lamar Blvd., Austin, TX 78756, USA.
Curr Opin Chem Biol. 2023 Apr;73:102277. doi: 10.1016/j.cbpa.2023.102277. Epub 2023 Mar 1.
The immune system presents a complex array of processes designed to maintain homeostasis in malignant cellular growth. Malignancy is the result of a breakdown in immune surveillance by cancer cells evading immune recognition. Significant efforts have been made in modulating immune checkpoint signaling cascades to bypass the resulting immune evasion and establish an anticancer effect. More recently, it was discovered that a form of regulated cell death can involve the stimulation of immune response as its downstream effect and subsequently re-establish immune surveillance. This mechanism, known as immunogenic cell death (ICD), is being exploited as a target to prevent tumor relapse and prevent cancer metastasis. It is now appreciated that metal-based compounds play a key role in ICD activation due to their unique biochemical properties and interactions within cancer cells. With fewer than 1% of known anticancer agents documented as ICD inducers, recent efforts have been made to identify novel entities capable of stimulating a more potent anticancer immune response. While the recent reviews by us or others focus primarily on either discussing the chemical library of ICD inducers or intricate detailing of biological pathways associated with ICD, this review aims to bridge these two topics as a concise summary. Furthermore, early clinical evidence and future directions of ICD are briefly summarized.
免疫系统呈现出一系列复杂的过程，旨在维持恶性细胞生长的体内平衡。恶性肿瘤是癌细胞逃避免疫识别导致免疫监视功能崩溃的结果。人们在调节免疫检查点信号级联方面付出了巨大努力，以绕过由此产生的免疫逃逸并建立抗癌效果。最近，人们发现一种形式的程序性细胞死亡可将刺激免疫反应作为其下游效应，随后重新建立免疫监视。这种机制被称为免疫原性细胞死亡（ICD），正被用作预防肿瘤复发和癌症转移的靶点。现在人们认识到，金属基化合物因其在癌细胞内独特的生化特性和相互作用，在ICD激活中发挥着关键作用。已知的抗癌药物中记录为ICD诱导剂的不到1%，最近人们努力寻找能够激发更强抗癌免疫反应的新物质。虽然我们或其他人最近的综述主要集中在讨论ICD诱导剂的化学文库或与ICD相关的生物途径的详细细节，但本综述旨在将这两个主题作为一个简明摘要进行衔接。此外，还简要总结了ICD的早期临床证据和未来方向。
