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Suppression of CD8+ T cells by the metabolite itaconate

Nature Metabolism volume 4, pages 1626–1627 (2022)Cite this article

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The immune-modulatory metabolite itaconate is secreted by myeloid-derived suppressor cells and taken up by CD8+ T cells to suppress their proliferation and function. In mice, blocking itaconate production enhances the efficacy of immune checkpoint blockade.

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Fig. 1: Immunofluorescence analysis of human melanoma tumours revealed IRG1 co-staining with the myeloid-derived suppressor cell (MDSC) marker LOX1.

References

  1. Veglia, F., Sanseviero, E. & Gabrilovich, D. I. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat. Rev. Immunol. 67, 485–498 (2021). A review article that presents the characteristics of MDSCs.

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  2. Kim, S. H. et al. Phenformin inhibits myeloid-derived suppressor cells and enhances the anti-tumor activity of PD-1 blockade in melanoma. J. Investig. Dermatol. 137, 1740–1748 (2017). This paper reports on the inhibitory effects of phenformin on MDSCs.

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  3. Hooftman, A. & O'Neill, L. A. J. The immunomodulatory potential of the metabolite itaconate. Trends Immunol. 40, 687–698 (2019). A review article that presents the immunomodulatory activities of itaconate and includes a timeline on the history of itaconate.

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  4. Michelucci, A. et al. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc. Natl Acad. Sci. USA 110, 7820–7825 (2013). This paper reports the discovery of IRG1 as the enzyme that catalyses the conversion of cis-aconitate to itaconic acid in mammals.

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This is a summary of: Zhao, H. et al. Myeloid-derived itaconate suppresses cytotoxic CD8+ T cells and promotes tumour growth. Nat. Metab. https://doi.org/10.1038/s42255-022-00676-9 (2022).

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Suppression of CD8+ T cells by the metabolite itaconate. Nat Metab 4, 1626–1627 (2022). https://doi.org/10.1038/s42255-022-00694-7

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