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Updated: Oct 10, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Immunogenic ferroptosis and where to find it?
Robin Demuynck1,2, Iuliia Efimova1,2, Faye Naessens1
1Cell Death Investigation and Therapy Lab, Department of Human Structure and Repair, Ghent University, Ghent, Belgium.
Abstract:
Ferroptosis is a recently discovered form of regulated cell death that is morphologically, genetically, and biochemically distinct from apoptosis and necroptosis, and its potential use in anticancer therapy is emerging. The strong immunogenicity of (early) ferroptotic cancer cells broadens the current concept of immunogenic cell death and opens up new possibilities for cancer treatment. In particular, induction of immunogenic ferroptosis could be beneficial for patients with cancers resistant to apoptosis and necroptosis. However, ferroptotic cancer cells may be a rich source of oxidized lipids, which contribute to decreased phagocytosis and antigen cross-presentation by dendritic cells and thus may favor tumor evasion. This could explain the non-immunogenicity of late ferroptotic cells. Besides the presence of lactate in the tumor microenvironment, acidification and hypoxia are essential factors promoting ferroptosis resistance and affecting its immunogenicity. Here, we critically discuss the crucial mediators controlling the immunogenicity of ferroptosis that modulate the induction of antitumor immunity. We emphasize that it will be necessary to also identify the tolerogenic (ie, immunosuppressive) nature of ferroptosis, which can lead to tumor evasion.
Insights
Ferroptosis, a distinct cell death form, shows potential in cancer therapy due to its immunogenicity. However, factors like oxidized lipids and tumor microenvironment conditions can lead to immune evasion.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Ferroptosis is a distinct form of regulated cell death.
- Its immunogenicity presents novel anticancer therapy opportunities, especially for apoptosis- and necroptosis-resistant cancers.
- However, ferroptotic cells can also promote tumor evasion through immunosuppressive mechanisms.
Purpose of the Study:
- To critically discuss mediators controlling ferroptosis immunogenicity.
- To explore how ferroptosis modulates antitumor immunity.
- To identify the tolerogenic nature of ferroptosis in tumor evasion.
Main Methods:
- Literature review and critical discussion of existing research on ferroptosis and immunogenic cell death.
- Analysis of factors influencing ferroptosis immunogenicity, including oxidized lipids and tumor microenvironment components.
- Exploration of the interplay between ferroptosis, dendritic cell function, and antitumor immunity.
Main Results:
- Early ferroptotic cancer cells exhibit strong immunogenicity, expanding the concept of immunogenic cell death.
- Oxidized lipids in ferroptotic cells can impair phagocytosis and antigen presentation, favoring tumor evasion.
- Tumor microenvironment factors like lactate, acidification, and hypoxia promote ferroptosis resistance and affect immunogenicity.
Conclusions:
- Inducing immunogenic ferroptosis offers a promising strategy for treating resistant cancers.
- Understanding and modulating ferroptosis's dual role in immunity and tolerance is crucial for effective cancer therapy.
- Further research is needed to harness ferroptosis for antitumor immunity while mitigating its immunosuppressive potential.
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