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Trefny, M.P.* ; Kroemer, G.* ; Zitvogel, L.* ; Kobold, S.

Metabolites as agents and targets for cancer immunotherapy.

Nat. Rev. Drug Discov., DOI: 10.1038/s41573-025-01227-z (2025)
Postprint Research data DOI PMC
Open Access Green
The depletion or accumulation of metabolites in the tumour microenvironment is one of the hallmarks of cancer, but targeting cancer cell metabolism therapeutically must also take into account the impact on metabolic pathways in immune cells. As we understand more about immunometabolism, opportunities arise for synergies between agents that modulate metabolism and immunotherapy. In this Review, we discuss the pivotal role of metabolic pathways in both cancer and immune cells in shaping the tumour microenvironment. We survey major anabolic and catabolic pathways and discuss how metabolic modulators and dietary nutrients can improve the anticancer immune response and overcome drug resistance mechanisms. Agents in the clinic include inhibitors of the adenosine and tryptophan pathways, and we discuss opportunities and challenges for successful drug development in the context of immune checkpoint blockade and chimeric antigen receptor (CAR)-T cell therapies.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords T-cell Metabolism; Aryl-hydrocarbon Receptor; Vitamin-d; Indoleamine 2,3-dioxygenase; Tumor Microenvironment; Immune Checkpoint; Dendritic Cells; Microbial Metabolites; Glutamine-metabolism; Antitumor Immunity
ISSN (print) / ISBN 1474-1776
Journal Nature Reviews - Drug Discovery
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Unit for Clinical Pharmacology (KKG-EKLiP)
Grants IdEx Universit de Paris
Bavarian Research Foundation
Fritz-Bender Foundation
European Research Council
Bundesministerium fr Bildung und Forschung
Wilhelm-Sander-Stiftung
German Cancer Aid
Else Krner-Fresenius-Stiftung
Horizon Programme of the EU
Marie Sklodowska-Curie Training Network for Optimizing Adoptive T Cell Therapy of Cancer - Horizon 2020 programme of the European Union
Deutsche Forschungsgemeinschaft (DFG)
Dr-Rurainski Foundation
Monika Kutzner Foundation
SNSF Postdoc.Mobility Fellowship
Institut National du Cancer
SIRIC
SIRIC Cancer Research and Personalized Medicine (CARPEM)
European Research Council Advanced Investigator Award
Seerave Foundation
ANR
Agence Nationale de la Recherche (ANR)
Agence Nationale de la Recherche under the France
European Union
Institut National du Cancer (INCa)
Ligue contre le Cancer
Bavarian Cancer Research Center (BZKF)