Bohn, Toszka, Rapp, Steffen, Luther, Natascha, Klein, Matthias, Bruehl, Till-Julius, Kojima, Nobuhiko, Lopez, Pamela Aranda, Hahlbrock, Jennifer, Muth, Sabine, Endo, Shogo, Pektor, Stefanie, Brand, Almut, Renner, Kathrin, Popp, Vanessa, Gerlach, Katharina, Vogel, Dennis, Lueckel, Christina, Arnold-Schild, Danielle, Pouyssegur, Jacques, Kreutz, Marina, Huber, Magdalena, Koenig, Jochem, Weigmann, Benno, Probst, Hans-Christian, von Stebut, Esther, Becker, Christian, Schild, Hansjoerg, Schmitt, Edgar and Bopp, Tobias (2018). Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages. Nat. Immunol., 19 (12). S. 1319 - 1333. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1529-2916

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Abstract

Many tumors evolve sophisticated strategies to evade the immune system, and these represent major obstacles for efficient antitumor immune responses. Here we explored a molecular mechanism of metabolic communication deployed by highly glycolytic tumors for immunoevasion. In contrast to colon adenocarcinomas, melanomas showed comparatively high glycolytic activity, which resulted in high acidification of the tumor microenvironment. This tumor acidosis induced Gprotein-coupled receptor-dependent expression of the transcriptional repressor ICER in tumor-associated macrophages that led to their functional polarization toward a non-inflammatory phenotype and promoted tumor growth. Collectively, our findings identify a molecular mechanism of metabolic communication between non-lymphoid tissue and the immune system that was exploited by high-glycolytic-rate tumors for evasion of the immune system.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bohn, ToszkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rapp, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luther, NataschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruehl, Till-JuliusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kojima, NobuhikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez, Pamela ArandaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahlbrock, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muth, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Endo, ShogoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pektor, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brand, AlmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Renner, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Popp, VanessaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerlach, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogel, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lueckel, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnold-Schild, DanielleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pouyssegur, JacquesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreutz, MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huber, MagdalenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenig, JochemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weigmann, BennoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Probst, Hans-ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Stebut, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schild, HansjoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmitt, EdgarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bopp, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-164115
DOI: 10.1038/s41590-018-0226-8
Journal or Publication Title: Nat. Immunol.
Volume: 19
Number: 12
Page Range: S. 1319 - 1333
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1529-2916
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SERUM LACTATE-DEHYDROGENASE; PROTEIN-COUPLED RECEPTORS; CAMP EARLY REPRESSOR; NF-KAPPA-B; LACTIC-ACID; INFLAMMATORY RESPONSES; SOLID TUMORS; IN-VITRO; IMMUNE; PROGRESSIONMultiple languages
ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16411

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