{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Vadevoo SMP"],"funding":["National Research Foundation of Korea"],"pagination":["e2102434118"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8449333"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["118(37)"],"pubmed_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."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages."],"pmcid":["PMC8449333"],"funding_grant_id":["2021R1A5A2021614","2017M3A9G8083382","2021R1A2C1009258","2019M3A9D5A01102797","2020M3A9D3038435"],"pubmed_authors":["Lee B","Lee C","Koo J","Lee N","Park JY","Chae S","Lee J","Gunassekaran GR","Vadevoo SMP"],"additional_accession":[]},"is_claimable":false,"name":"The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages.","description":"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.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2025-04-04T10:21:14.183Z","creation":"2025-04-04T10:21:14.183Z"},"accession":"S-EPMC8449333","cross_references":{"pubmed":["34504016"],"doi":["10.1073/pnas.2102434118"]}}