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The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages

Title
The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages
Authors
Vadevoo, Sir Murugan PoongkavithaiGunassekaran, Gowri RangaswarmyLee, ChaeEunLee, NaHyeLee, JiyounChae, SehyunPark, Jae-YongKoo, JaeHyungLee, Byungheon
DGIST Authors
Vadevoo, Sir Murugan Poongkavithai; Gunassekaran, Gowri Rangaswarmy; Lee, ChaeEun; Lee, NaHye; Lee, Jiyoun; Chae, Sehyun; Park, Jae-Yong; Koo, JaeHyung; Lee, Byungheon
Issue Date
2021-09
Citation
Proceedings of the National Academy of Sciences of the United States of America, 118(37)
Type
Article
Author Keywords
TAMsGPCRLactateOlfr78OR51E2
Keywords
PROTEIN-COUPLED RECEPTORSOLFACTORY RECEPTORACTIVATIONPOLARIZATIONEXPRESSIONDEPLETIONTARGETSGROWTHGENEG2A
ISSN
0027-8424
Abstract
Expression and function of odorant receptors (ORs), which account for more than 50% of G protein-coupled receptors, are being increasingly reported in nonolfactory sites. However, ORs that can be targeted by drugs to treat diseases remain poorly identified. Tumorderived lactate plays a crucial role in multiple signaling pathways leading to generation of tumor-associated macrophages (TAMs). In this study, we hypothesized that the macrophage OR Olfr78 functions as a lactate sensor and shapes the macrophage-tumor axis. Using Olfr78+/+ and Olfr78-/- bone marrow-derived macrophages with or without exogenous Olfr78 expression, we demonstrated that Olfr78 sensed tumor-derived lactate, whichwas themain factor in tumor-conditioned media responsible for generation of protumoral M2-TAMs. Olfr78 functioned together with Gpr132 to mediate lactate-induced generation of protumoral M2-TAMs. In addition, syngeneic Olfr78-deficient mice exhibited reduced tumor progression and metastasis together with an increased anti- versus protumoral immune cell population. We propose that the Olfr78-lactate interaction is a therapeutic target to reduce and prevent tumor progression and metastasis. © 2021 National Academy of Sciences. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/15460
DOI
10.1073/pnas.2102434118
Publisher
National Academy of Sciences
Related Researcher
  • Author Koo, JaeHyung Brain-Immune Axis Laboratory
  • Research Interests 장내미생물/감염균 유래 대사체를 통한 신경염증, 알츠하이머병, 우울증, 당뇨/비만, 대사체/수용체 상호작용에 의한 대사연구
Files:
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Collection:
Department of New BiologyBrain-Immune Axis Laboratory1. Journal Articles


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