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Nat Immunol. 2018 Dec;19(12):1319-1329. doi: 10.1038/s41590-018-0226-8. Epub 2018 Nov 5.

Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages.

Author information

1
Institute for Immunology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
2
Molecular Genetics, Johannes Gutenberg University Mainz, Mainz, Germany.
3
Dermatology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.
4
Faculty of Life Sciences, Toyo University, Gunma, Japan.
5
Third Medical Clinic, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.
6
Aging Neuroscience Research Team, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
7
Department of Nuclear Medicine, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.
8
Internal Medicine III, University of Regensburg, Regensburg, Germany.
9
Regensburg Center for Immunology (RCI), Regensburg, Germany.
10
Department of Medicine 1, University of Erlangen-N├╝rnberg, Erlangen, Germany.
11
Institute for Medical Microbiology and Hospital Hygiene, University of Marburg, Marburg, Germany.
12
Institute of Research on Cancer and Aging, University of Nice-Sophia Antipolis, Nice, France.
13
Medical Biology Department, Centre Scientifique de Monaco (CSM), Monaco, Monaco.
14
Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.
15
Research Center for Immunotherapy (FZI), University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.
16
Dermatology and Venereology, University Medical Center Cologne, Cologne, Germany.
17
University Cancer Center, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.
18
Institute for Immunology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany. boppt@uni-mainz.de.
19
Research Center for Immunotherapy (FZI), University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany. boppt@uni-mainz.de.
20
University Cancer Center, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany. boppt@uni-mainz.de.
21
German Cancer Consortium (DKTK), Heidelberg, Germany. boppt@uni-mainz.de.

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.

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PMID:
30397348
DOI:
10.1038/s41590-018-0226-8
[Indexed for MEDLINE]

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