Iron Boosts Antitumor Type 1 T-cell Responses and Anti-PD1 Immunotherapy - Archive ouverte HAL
Article Dans Une Revue Cancer Immunology Research Année : 2024

Iron Boosts Antitumor Type 1 T-cell Responses and Anti-PD1 Immunotherapy

Sarah Porte
Christian Wu
Aurélie Durand
Théo Level
Léa Giraud
Amélie Lombès
Mathieu Germain
Rémi Pierre
Benjamin Saintpierre
Mireille Lambert
Cédric Auffray
Carole Peyssonnaux
Sophie Vaulont
Marie-Clotilde Alves-Guerra
Renaud Dentin
Bruno Lucas
Bruno Martin
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Résumé

Cancers only develop if they escape immunosurveillance, and the success of cancer immunotherapies relies in most cases on their ability to restore effector T-cell functions, particularly IFNγ production. Revolutionizing the treatment of many cancers, immunotherapies targeting immune checkpoints such as PD1 can increase survival and cure patients. Unfortunately, although immunotherapy has greatly improved the prognosis of patients, not all respond to anti-PD1 immunotherapy, making it crucial to identify alternative treatments that could be combined with current immunotherapies to improve their effectiveness. Here, we show that iron supplementation significantly boosts T-cell responses in vivo and in vitro. The boost was associated with a metabolic reprogramming of T cells in favor of lipid oxidation. We also found that the “adjuvant” effect of iron led to a marked slowdown of tumor cell growth after tumor cell line transplantation in mice. Specifically, our results suggest that iron supplementation promotes antitumor responses by increasing IFNγ production by T cells. In addition, iron supplementation improved the efficacy of anti-PD1 cancer immunotherapy in mice. Finally, our study suggests that, in patients with cancer, the quality and efficacy of the antitumor response following anti-PD1 immunotherapy may be modulated by plasma ferritin levels. In summary, our results suggest the benefits of iron supplementation on the reactivation of antitumor responses and support the relevance of a fruitful association between immunotherapy and iron supplementation.
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Dates et versions

hal-04736166 , version 1 (14-10-2024)

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Citer

Sarah Porte, Alexandra Audemard-Verger, Christian Wu, Aurélie Durand, Théo Level, et al.. Iron Boosts Antitumor Type 1 T-cell Responses and Anti-PD1 Immunotherapy. Cancer Immunology Research, 2024, 12 (9), pp.1252-1267. ⟨10.1158/2326-6066.CIR-23-0739⟩. ⟨hal-04736166⟩
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