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

Bohn T, Rapp S, Luther N, Klein M, Bruehl TJ, Kojima N, Lopez PA, Hahlbrock J, Muth S, Endo S, Pektor S, Brand A, Renner K, Popp V, Gerlach K, Vogel D, Lueckel C, Arnold-Schild D, Pouyssegur J, Kreutz M, Huber M, Koenig J, Weigmann B, Probst HC, Von Stebut E, Becker C, Schild H, Schmitt E, Bopp T (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Nature Immunology Nature Research

Book Volume: 19

Pages Range: 1319-1329

Journal Issue: 12

DOI: 10.1038/s41590-018-0226-8

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.

Authors with CRIS profile

Vanessa Popp Institute of Radiology Katharina Gerlach Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Benno Weigmann Medizinische Fakultät

Involved external institutions

Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE) Toyo University JP Japan (JP) Tokyo Metropolitan Institute of Gerontology JP Japan (JP) Universität Regensburg DE Germany (DE) Philipps-Universität Marburg DE Germany (DE) University of Nice Sophia Antipolis / Université Nice Sophia Antipolis FR France (FR) Universitätsklinikum Köln DE Germany (DE)

How to cite

APA:

Bohn, T., Rapp, S., Luther, N., Klein, M., Bruehl, T.-J., Kojima, N.,... Bopp, T. (2018). Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages. Nature Immunology, 19(12), 1319-1329. https://doi.org/10.1038/s41590-018-0226-8

MLA:

Bohn, Toszka, et al. "Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages." Nature Immunology 19.12 (2018): 1319-1329.

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