In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 37 ( 2021-09-14)
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. Tumor-derived 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, which was the main 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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.2102434118
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2021
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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