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Tumour immunology

Suppressive metabolites

Nature Reviews Immunology volume 16, page 659 (2016)Cite this article

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To investigate whether lactic acid could compromise tumour immunosurveillance, the authors used a melanoma model to compare the growth rate of mouse melanoma B16.SIY cells with reduced levels of Ldha (LDHAlow) in immunocompetent (C57BL/6) versus immunodeficient (Rag2−/−gc−/−) mice. LDHAlow tumours, which secreted less lactate, grew at a slower rate and with increased infiltration of T cells and natural killer (NK) cells in immunocompetent mice than control tumours (formed from B16.SIY cells with comparatively higher levels of Ldha expressed). By contrast, in Rag2−/−gc−/− mice LDHAlow and control tumours developed at the same rate, indicating that immune cell infiltration of LDHAlow tumours is effective at limiting tumour expansion. Interestingly, this effect of tumour-induced lactic acid production on the immune cell infiltration seems to be restricted to the local tumour environment, as the composition of immune cells in the blood and spleen of LDHAlow tumour-bearing mice was unchanged.

tumour-derived lactic acid could perturb cytokine production of tumour-infiltrating T and NK cells

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References

  1. Brand, A. et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab. https://dx.doi.org/10.1016/j.cmet.2016.08.011 (2016)

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  1. Locum Associate Editor, Nature Reviews Cancer,

    Anna Dart

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  1. Anna Dart
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Dart, A. Suppressive metabolites. Nat Rev Immunol 16, 659 (2016). https://doi.org/10.1038/nri.2016.119

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