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KIDNEY CANCER

IL-23 links glutamine addiction and immune function

Nature Reviews Urology volume 15, page 725 (2018)Cite this article

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A key metabolic hallmark of clear cell renal cell carcinoma (ccRCC) is glutamine addiction, which depletes the local microenvironment of this metabolite. However, the influence of tumour glutamine metabolism on the ccRCC immune contexture is unclear. A new study now offers mechanistic insight into how macrophage-derived interleukin-23 (IL-23) orchestrates immune infiltration in glutamine-addicted ccRCC tumours.

The role of IL-23 in regulating Treg cell function was then investigated. In co-culture experiments, recombinant IL-23 treatment increased Treg cell proliferation and activation, elevated Treg cell-derived transforming growth factor-β (TGFβ) and IL-10 expression, and enhanced Treg cell-dependent suppression of responder CD4+ and CD8+ T cell proliferation, inferring that IL-23 enhances Treg cell immunosuppressive functionality. Flow cytometry and immunofluorescence assays identified macrophages as the predominant source of IL-23 in human ccRCC tumours. Furthermore, culture of murine peritoneal macrophages and isolated human tumour-infiltrating macrophages under glutamine-deficient conditions increased IL-23 secretion, suggesting that glutamine deprivation in the glutamine-addicted ccRCC tumour microenvironment promotes IL-23 secretion. Subsequent experiments identified a role for hypoxia-inducible factor 1α (HIF1α) in IL-23 induction in glutamine-deprived macrophages.

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  1. Nature Reviews Urology http://www.nature.com/nrurol/

    Conor A. Bradley

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  1. Conor A. Bradley
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Correspondence to Conor A. Bradley.

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Bradley, C.A. IL-23 links glutamine addiction and immune function. Nat Rev Urol 15, 725 (2018). https://doi.org/10.1038/s41585-018-0118-6

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