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The immunometabolic ecosystem in cancer

Nature Immunology volume 24, pages 2008–2020 (2023)Cite this article

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Abstract

Our increased understanding of how key metabolic pathways are activated and regulated in malignant cells has identified metabolic vulnerabilities of cancers. Translating this insight to the clinics, however, has proved challenging. Roadblocks limiting efficacy of drugs targeting cancer metabolism may lie in the nature of the metabolic ecosystem of tumors. The exchange of metabolites and growth factors between cancer cells and nonmalignant tumor-resident cells is essential for tumor growth and evolution, as well as the development of an immunosuppressive microenvironment. In this Review, we will examine the metabolic interplay between tumor-resident cells and how targeted inhibition of specific metabolic enzymes in malignant cells could elicit pro-tumorigenic effects in non-transformed tumor-resident cells and inhibit the function of tumor-specific T cells. To improve the efficacy of metabolism-targeted anticancer strategies, a holistic approach that considers the effect of metabolic inhibitors on major tumor-resident cell populations is needed.

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Fig. 1: The metabolic ecosystem of tumors.
Fig. 2: Key components of mitochondrial metabolism in cancer.
Fig. 3: Metabolic rewiring in pancreatic cancer-resident cells and T cells following treatment with CPI-613.
Fig. 4: Glutamine metabolism in the ccRCC microenvironment.

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Authors and Affiliations

  1. Department of Biomedicine, Immunobiology, University of Basel and University Hospital of Basel, Basel, Switzerland

    Glenn R. Bantug & Christoph Hess

  2. Department of Medicine, CITIID, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK

    Christoph Hess

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G.R.B. and C.H. jointly conceived and wrote this review.

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Bantug, G.R., Hess, C. The immunometabolic ecosystem in cancer. Nat Immunol 24, 2008–2020 (2023). https://doi.org/10.1038/s41590-023-01675-y

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