巨噬细胞
癌症研究
肿瘤进展
受体
转移
免疫系统
生物
人口
M2巨噬细胞
肿瘤微环境
表型
免疫学
医学
体外
内科学
癌症
生物化学
基因
环境卫生
作者
Sri Murugan Poongkavithai Vadevoo,Gowri Rangaswamy Gunassekaran,ChaeEun Lee,NaHye Lee,Jiyoun Lee,Sehyun Chae,Jae Yong Park,Jae Hyung Koo,Byungheon Lee
标识
DOI:10.1073/pnas.2102434118
摘要
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.
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