Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity

Bartosz Wiernicki, Sophia Maschalidi, Jonathan Pinney, Sandy Adjemian, Tom Vanden Berghe, Kodi S. Ravichandran, Peter Vandenabeele

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Immunogenic cell death significantly contributes to the success of anti-cancer therapies, but immunogenicity of different cell death modalities widely varies. Ferroptosis, a form of cell death that is characterized by iron accumulation and lipid peroxidation, has not yet been fully evaluated from this perspective. Here we present an inducible model of ferroptosis, distinguishing three phases in the process—‘initial’ associated with lipid peroxidation, ‘intermediate’ correlated with ATP release and ‘terminal’ recognized by HMGB1 release and loss of plasma membrane integrity—that serves as tool to study immune cell responses to ferroptotic cancer cells. Co-culturing ferroptotic cancer cells with dendritic cells (DC), reveals that ‘initial’ ferroptotic cells decrease maturation of DC, are poorly engulfed, and dampen antigen cross-presentation. DC loaded with ferroptotic, in contrast to necroptotic, cancer cells fail to protect against tumor growth. Adding ferroptotic cancer cells to immunogenic apoptotic cells dramatically reduces their prophylactic vaccination potential. Our study thus shows that ferroptosis negatively impacts antigen presenting cells and hence the adaptive immune response, which might hinder therapeutic applications of ferroptosis induction.

Original languageEnglish
Article number3676
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

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