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A dynamic metabolic flux analysis of myeloid-derived suppressor cells confirms immunosuppression-related metabolic plasticity

Guillaume Goffaux, Iness Hammami and Mario Jolicoeur

Article (2017)

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Cite this document: Goffaux, G., Hammami, I. & Jolicoeur, M. (2017). A dynamic metabolic flux analysis of myeloid-derived suppressor cells confirms immunosuppression-related metabolic plasticity. Scientific Reports, 7(1). doi:10.1038/s41598-017-10464-1
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Abstract

Recent years have witnessed an increasing interest at understanding the role of myeloid-derived suppressor cells (MDSCs) in cancer-induced immunosuppression, with efforts to inhibit their maturation and/or their activity. We have thus modelled MDSCs central carbon metabolism and bioenergetics dynamic, calibrating the model using experimental data on in vitro matured mice bone marrow cells into MDSCs. The model was then used to probe the cells metabolic state and dynamics, performing a dynamic metabolic flux analysis (dMFA) study. Indeed, MDSCs maturation correlates with a high glycolytic flux contributing to up to 95% of the global ATP turnover rate, while most of the glucose-derived carbon enters the TCA cycle. Model simulations also reveal that pentose phosphate pathway and oxidative phosphorylation activities were kept at minimal levels to ensure NADPH production and anabolic precursors synthesis. Surprisingly, MDSCs immunosuppressive activity, i.e. L-arginine uptake, metabolism and endogenous synthesis, only consumes sparse quantities of energy-rich nucleotides (ATP and NADPH). Therefore, model simulations suggest that MDSCs exhibit a heterogeous metabolic profile similar to tumour cells. This behavior is probably an indirect immunosuppressive mechanism where MDSCs reduce the availability of carbon sources in the tumour periphery microenvironment, which could explain the dysfuntion and death of immune effector cells.

Open Access document in PolyPublie
Subjects: 1800 Génie chimique > 1802 Génie biochimique
1900 Génie biomédical > 1900 Génie biomédical
9000 Sciences de la santé > 9000 Sciences de la santé
Department: Département de génie chimique
Research Center: Autre
Funders: CRSNG/NSERC
Grant number: 093865
Date Deposited: 26 Mar 2020 16:07
Last Modified: 27 Mar 2020 01:20
PolyPublie URL: https://publications.polymtl.ca/3590/
Document issued by the official publisher
Journal Title: Scientific Reports (vol. 7, no. 1)
Publisher: Springer Nature
Official URL: https://doi.org/10.1038/s41598-017-10464-1

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