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Comment
. 2021 Apr 30;6(1):171.
doi: 10.1038/s41392-021-00598-0.

Lactate-avid regulatory T cells: metabolic plasticity controls immunosuppression in tumour microenvironment

Gabriele Multhoff  1   2 , Peter Vaupel  3   4
Affiliations
Comment

Lactate-avid regulatory T cells: metabolic plasticity controls immunosuppression in tumour microenvironment

Gabriele Multhoff et al. Signal Transduct Target Ther. .
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Effects of glycolysis-derived extracellular lactic acid on the plasticity of regulatory T (Treg) cells. To maintain energy homoeostasis, tumour cells have an enhanced glycolytic flux. Glucose import is mediated by an overexpression of GLUT1/3 transporters under normoxic (Warburg effect) and hypoxic (anaerobic glycolysis) conditions. Especially under hypoxia glucose is metabolized via phosphoenolpyruvate (PEP) into pyruvate by glycolysis and does not enter the tricarboxylic acid (TCA, Krebs) cycle and undergoes oxidative phosphorylation (OxPhos). Pyruvate is converted into lactate anion (Lactate-) and gets imported/exported via MCT1/4 symporters. High extracellular lactate- levels contribute to an acidification (pH <6.9) of the tumour microenvironment (TME), stimulate the expression of the immune checkpoint inhibitor ligand PDL1 on tumour cells, and serve as a fuel for lactate-avid Treg cells. Lactate-avid Treg cells express higher numbers (associated with a higher activity) of the lactate importer MCT1, show an enhanced lactate dehydrogenase A (LDHA) activity, and immunosuppressive capacity compared to glucose-avid Treg cells. In this simplified scheme only transporters and enzymes relevant for the highlight report are illustrated. (GLUT1/3 glucose-transporter 1/3, LDHA lactate dehydrogenase A, MCT1/4 lactate importer/exporter, OxPhos oxidative phosphorylation, PEP, phosphoenolpyruvate, PDL1 immune checkpoint inhibitor ligand of PD-1, TCA tricarboxylic acid, TME tumour microenvironment.)
See this image and copyright information in PMC

Comment on

  • Metabolic support of tumour-infiltrating regulatory T cells by lactic acid.
    Watson MJ, Vignali PDA, Mullett SJ, Overacre-Delgoffe AE, Peralta RM, Grebinoski S, Menk AV, Rittenhouse NL, DePeaux K, Whetstone RD, Vignali DAA, Hand TW, Poholek AC, Morrison BM, Rothstein JD, Wendell SG, Delgoffe GM. Watson MJ, et al. Nature. 2021 Mar;591(7851):645-651. doi: 10.1038/s41586-020-03045-2. Epub 2021 Feb 15. Nature. 2021. PMID: 33589820 Free PMC article.

References

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