PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Baumann, T.* ; Dunkel, A.* ; Schmid, C.* ; Schmitt, S.* ; Hiltensperger, M.* ; Lohr, K.* ; Laketa, V.* ; Donakonda, S.* ; Ahting, U.* ; Lorenz-Depiereux, B. ; Heil, J.E.* ; Schredelseker, J.* ; Simeoni, L.* ; Fecher, C.* ; Körber, N. ; Bauer, T. ; Hüser, N.* ; Hartmann, D.* ; Laschinger, M.* ; Eyerich, K.* ; Eyerich, S. ; Anton, M.* ; Streeter, M.* ; Wang, T.* ; Schraven, B.* ; Spiegel, D.* ; Assaad, F.* ; Misgeld, T.* ; Zischka, H. ; Murray, P.J.* ; Heine, A.* ; Heikenwälder, M.* ; Korn, T.* ; Dawid, C.* ; Hofmann, T.* ; Knolle, P.A.* ; Höchst, B.*

Regulatory myeloid cells paralyze T cells through cell-cell transfer of the metabolite methylglyoxal.

Nat. Immunol. 21, 555-566 (2020)
Postprint Forschungsdaten DOI PMC
Open Access Green
Regulatory myeloid immune cells, such as myeloid-derived suppressor cells (MDSCs), populate inflamed or cancerous tissue and block immune cell effector functions. The lack of mechanistic insight into MDSC suppressive activity and a marker for their identification has hampered attempts to overcome T cell inhibition and unleash anti-cancer immunity. Here, we report that human MDSCs were characterized by strongly reduced metabolism and conferred this compromised metabolic state to CD8(+) T cells, thereby paralyzing their effector functions. We identified accumulation of the dicarbonyl radical methylglyoxal, generated by semicarbazide-sensitive amine oxidase, to cause the metabolic phenotype of MDSCs and MDSC-mediated paralysis of CD8(+) T cells. In a murine cancer model, neutralization of dicarbonyl activity overcame MDSC-mediated T cell suppression and, together with checkpoint inhibition, improved the efficacy of cancer immune therapy. Our results identify the dicarbonyl methylglyoxal as a marker metabolite for MDSCs that mediates T cell paralysis and can serve as a target to improve cancer immune therapy.Myeloid-derived suppressor cells (MDSCs) residing within tumors can impede immune responses. Knolle and colleagues show that MDSCs poison immune cells by producing methylglyoxal, which functionally alters their cellular metabolism and hence their effector responses.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
20.479
3.703
62
79
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hepatocellular-carcinoma Patients; Suppressor-cells; Dicarbonyl Stress; Amine Oxidase; Effector; Immunotherapy; Aminoacetone; Inhibition; Glycation; Proteins
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Zeitschrift Nature Immunology
Quellenangaben Band: 21, Heft: 5, Seiten: 555-566 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort 75 Varick St, 9th Flr, New York, Ny 10013-1917 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
Institute of Virology (VIRO)
Institute for Allergy Research (IAF)
Institute of Molecular Toxicology and Pharmacology (TOX)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30203 - Molecular Targets and Therapies
30202 - Environmental Health
Forschungsfeld(er) Genetics and Epidemiology
Immune Response and Infection
Allergy
Enabling and Novel Technologies
PSP-Element(e) G-500700-001
G-502700-003
G-502700-002
G-505490-001
G-505200-003
DOI 10.1038/s41590-020-0666-9
WOS ID WOS:000528265700018
Scopus ID 85083841278
PubMed ID 32327756
Erfassungsdatum 2020-05-15
[➜Korrektur melden]