Immunogenic cell death pathways and tumor-immune interface (ICD)

Immunogenic cell death (ICD) is a form of regulated cell death that is capable of eliciting a systemic, long-term immune response against antigens derived from the dying cell. Unlike physiological apoptosis, which is typically non-immunogenic or even tolerogenic, ICD is characterized by the emission of damage-associated molecular patterns (DAMPs) such as calreticulin, HMGB1, and ATP (Galluzzi et al., 2017, Nature Reviews Immunology). These signals act as 'eat-me' and 'find-me' cues for innate immune cells, particularly dendritic cells, which then process tumor antigens and prime cytotoxic T lymphocytes within the tumor-immune interface (Kroemer et al., 2013, Annual Review of Immunology). In the context of oncology, the tumor-immune interface represents the dynamic site of interaction between malignant cells and the host immune system, where the success of ICD can determine the efficacy of various therapeutic interventions. Many conventional anticancer agents, including specific chemotherapies like doxorubicin and oxaliplatin, as well as radiotherapy, exert their long-term effects by inducing ICD and converting the tumor into an 'in situ' vaccine (Galluzzi et al., 2020, Nature Reviews Molecular Cell Biology). Understanding these pathways is critical for developing combinatorial strategies that enhance the immunogenicity of 'cold' tumors and overcome the immunosuppressive barriers of the tumor microenvironment.

Other names

Immunogenic cell deathICD pathwaysDAMP-mediated immune activationImmunogenic apoptosis

Induction of endoplasmic reticulum stress and reactive oxygen species leading to the exposure and release of damage-associated molecular patterns (DAMPs) that activate the adaptive immune system.