Investigating the immunoregulatory properties of ferroptosis in experimental cancer models

01 November 2020 → 31 October 2024
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Cancer biology
    • Cell death
    • Cancer therapy
Immunogenic cell death cancer biology ferroptosis
Project description

Immunogenic cell death (ICD) is a phenomenon in which cancer cell death results in activation of adaptive anti-tumor immunity. The emergence of the concept of ICD has opened the avenue for development of novel anti-cancer strategies. Besides induction of immunogenic apoptosis and necroptosis, now induction of ferroptosis has been suggested to be a promising novel anti-cancer strategy to treat therapy-resistant cancer cells. Nevertheless, little is known on the immunogenic nature of ferroptosis. Research performed in our unit has now demonstrated in vitro and by prophylactic vaccination in vivo that ferroptotic cell death might elicit immunosuppressive responses and possibly result in exacerbated tumor growth. Moreover, we have also demonstrated that prophylactic vaccination with mixtures of apoptotic and ferroptotic cancer cells, results in a higher tumor prevalence than apoptotic cells alone, after a re-challenge with live tumor cells. This apparent dominant immunosuppressive property of ferroptosis might have great therapeutic implications since the majority of chemo- and radiotherapeutic treatments induce mixtures of cell death modalities, including ferroptosis. In this project, we aim to elucidate the mechanisms of immunosuppression by ferroptosis and further investigate our findings in a syngeneic, orthotopic colon carcinoma model. Additionally, we will investigate whether inhibiting lipid peroxidation during radiotherapy might increase the immunogenic responses