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

Toszka Bohn, Steffen Rapp, Natascha Luther, Matthias Klein, Till-Julius Brühl, Nobuhiko Kojima, Pamela Aranda Lopez, Jennifer Hahlbrock, Sabine Muth, Shogo Endo, Stefanie Pektor, Almut Brand, Kathrin Renner, Vanessa Popp, Katharina Gerlach, Dennis Vogel, Christina Lückel, Danielle Arnold-Schild, Jacques Pouysségur, Marina Kreutz, Magdalena Huber, Jochem König, Benno Weigmann, Hans Christian Probst, Esther Von Stebut … & Tobias Bopp
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...
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