Ferroptosis-armed dendritic cell vaccines for glioma immunotherapy PMID: 42098128

ADC Targets in Oncology

2026-04-10

Ferroptosis-armed dendritic cell vaccines for glioma immunotherapy

Nat Commun. 2026 May 7. doi: 10.1038/s41467-026-72737-6.

Mariia Saviuk ¹ ² , Victoria D Turubanova ¹ ³ , Sara De Brée ¹ ² , Sandra Van Lint ² ⁴ , Teresa Mendes Maia ⁵ ⁶ ⁷ , Simon Devos ⁵ ⁶ ⁷ , Iuliia Efimova ¹ ² , Julie Braet ² ⁴ , Lore Van Oudenhove ⁸ , Gitta Boons ⁸ , Faye Naessens ¹ ² , Robin Demuynck ¹ ² , Ellen Saeys ¹ ² , Christian Vanhove ⁹ , Lukas Bunse ¹⁰ ¹¹ , Peter M van Endert ¹² ¹³ , Robrecht Raedt ¹⁴ , Maria V Vedunova ¹⁵ , Olga Krysko ¹ , Roosmarijn E Vandenbroucke ¹⁶ ¹⁷ , Karim Vermaelen ² ⁴ , Tatiana A Mishchenko ¹⁵ , Elena Catanzaro ^# ¹⁸ ¹⁹ , Dmitri V Krysko ^# ¹ ²

Affiliations

1. 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.
2. Cancer Research Institute Ghent, Ghent, Belgium.
3. Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod, Nizhny, Russia.
4. Thoracic Tumor Immunology Laboratory (TTIL), Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Science, Ghent University, Ghent, Belgium.
5. VIB Proteomics Core, VIB, Ghent, Belgium.
6. VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
7. Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
8. myNEO Therapeutics, Ghent, Belgium.
9. IBiTech-MEDISIP-Infinity Laboratory, Department of Electronics and Information Systems, Faculty of Engineering and Architecture, Ghent University, Ghent, Belgium.
10. Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
11. Neurology Clinic, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany.
12. Université Paris Cité, INSERM, CNRS, Institut Necker Enfants Malades, Paris, France.
13. Service Immunologie Biologique, AP-HP, Hôpital Universitaire Necker-Enfants Malades, Paris, France.
14. 4Brain, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
15. Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny Novgorod, Nizhny, Russia.
16. VIB Center for Inflammation Research, Ghent, Belgium.
17. Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University, Ghent, Belgium.
18. 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. [email protected].
19. Cancer Research Institute Ghent, Ghent, Belgium. [email protected].
# Contributed equally.

Abstract

The type of cell death has proven to play a crucial role in Cancer Immunotherapy efficacy. Immunogenic cell death (ICD) enhances tumor adjuvanticity and antigenicity by releasing danger signals and altering the immune peptidome. The immunogenicity of Ferroptosis, an iron-dependent form of cell death, remains uncertain. Here, we show that dendritic cell (DC) vaccines loaded with ferroptotic lysates protect mice against glioma growth, inducing IFN-γ production, and promoting robust CD8⁺ T cell infiltration, activation, and effector memory formation in the tumor microenvironment. The intrinsic immunogenicity of Ferroptosis was independent of the glioma type and the Ferroptosis inducer. Instead, it critically required the presence of the damage-associated molecular patterns calreticulin and ATP, rather than involving HMGB1-TLR4 signaling. However, supplementing these DAMPs into DC vaccines loaded with non-ICD lysates did not restore efficacy to the level of the ferroptosis-based DC vaccine, suggesting a more complex mechanism beyond a purely DAMP-mediated effect. These findings demonstrate that ferroptosis-loaded DC vaccines elicit a potent, tumor-specific immune response, capable of eradicating intracranial gliomas in mice, which highlights their potential in Cancer Immunotherapy.