Immunogenicity of ferroptosis in cancer: a matter of context?

Trends Cancer

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. Electronic address:

Published: May 2024

Ferroptosis is a variant of regulated cell death (RCD) elicited by an imbalance of cellular redox homeostasis that culminates with extensive lipid peroxidation and rapid plasma membrane breakdown. Since other necrotic forms of RCD, such as necroptosis, are highly immunogenic, ferroptosis inducers have attracted considerable attention as potential tools to selectively kill malignant cells while eliciting therapeutically relevant tumor-targeting immune responses. However, rather than being consistently immunogenic, ferroptosis mediates context-dependent effects on anticancer immunity. The inability of ferroptotic cancer cells to elicit adaptive immune responses may arise from contextual deficiencies in intrinsic aspects of the process, such as adjuvanticity and antigenicity, or from microenvironmental defects imposed by ferroptotic cancer cells themselves or elicited by the induction of ferroptosis in immune cells.

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Source
http://dx.doi.org/10.1016/j.trecan.2024.01.013DOI Listing

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