Immunogenic cell death-inducing metal complexes: From the benchtop to the clinic

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 surveil-lance 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 mecha-nism, 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 docu-mented 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 li-brary of ICD inducers or intricate detailing of biological path-ways associated with ICD, this review aims to bridge these two topics as a concise summary. Furthermore, early clinical evi-dence and future directions of ICD are briefly summarized.

Automated summary

The immune system plays a vital role in maintaining homeostasis and preventing the growth of malignant cells. Immune evasion by cancer cells is a major challenge, but efforts have been made to activate the immune response through immunogenic cell death (ICD) and metal-based compounds. The development of novel ICD inducers and understanding the biological pathways associated with ICD are important for enhancing anticancer immune responses. This review provides a concise summary of these topics and discusses the early clinical evidence and future directions of ICD.