Myeloid-derived suppressor cells (MDSC) transmitted the metabolite methylglyoxal to CD8+ T cells.

  • Major Finding: Myeloid-derived suppressor cells (MDSC) transmitted the metabolite methylglyoxal to CD8+ T cells.

  • Mechanism: Methylglyoxal reduced T-cell activity by depleting free L-arginine, reducing antitumor efficacy.

  • Impact: Methylglyoxal is an MDSC marker that plays a role in MDSC-mediated immunosuppression in cancer.


Myeloid-derived suppressor cells (MDSC) are regulatory immune cells that are associated with sites of chronic inflammation and cancer and suppress CD8+ T-cell function. However, the mechanism by which MDSCs regulate cytotoxic T-cell function is unclear, and a lack of molecular markers to definitively identify cells as MDSCs has hindered research on this topic. Baumann and colleagues found that MDSCs had very low metabolism compared with the monocytes from which they were derived. Additional experiments revealed that MDSCs caused suppression of activation-induced signaling in CD8+ T cells and caused these cytotoxic T lymphocytes to fail to increase glycolysis and effector function. Notably, this process was dependent on cell–cell contact between MDSCs and CD8+ T cells, and there was evidence of transfer of cytosolic contents from MDSCs to CD8+ T cells. Deeper investigation uncovered a buildup of the α-dicarbonyl radical methylglyoxal in MDSCs, and this chemical contributed to the low metabolism of MDSCs. In MDSCs, methylglyoxal was derived from aminoacetone (also known as 1-amino-2-propanone), a catabolite of threonine and glycine, via oxidation by semicarbazide-sensitive amine oxidase (also known as primary-amine oxidase), an enzyme that catalyzes conversion between primary amines and their corresponding aldehydes. Further, this methylglyoxal was transferred from MDSCs to CD8+ T cells within minutes of cell–cell contact and contributed to reduced T-cell function, an effect mediated by glycation-induced depletion of free L-arginine (with which methylglyoxal reacts to form advanced glycation end products) in T cells. Because L-arginine is required for T-cell activation, this L-arginine depletion may account for the reduced T-cell function observed after contact with MDSCs. Finally, combined treatment with the immune-checkpoint inhibitor anti–PD-1 and dimethylbiguanide, which blocks the suppressive effects of MDSCs on CD8+ T cells, caused tumor regression in a mouse model of melanoma. In summary, this work identifies methylglyoxal as a key marker and potential therapeutic target that can be used to distinguish MDSCs from other cells and specifies the role of this compound in MDSC-mediated suppression of CD8+ T-cell function in cancer.

Baumann T, Dunkel A, Schmid C, Schmitt S, Hiltensperger M, Lohr K, et al. Regulatory myeloid cells paralyze T cells through cell–cell transfer of the metabolite methylglyoxal. Nat Immunol 2020;21:555–66.

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