Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression (Nat Commun. 2018, 9(1):2574.)

報告日期: 2018/10/26
報告時間: 16:00/16:50
報告學生: 林羽珊
講評老師: 陳百昇
附件下載: 下載[1748-1538016205-1.pdf] 

Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression

Wei Xiang, Rongchen Shi, Xia Kang, Xuan Zhang, Peng Chen, Lili Zhang, Along Hou, Rui Wang, Yuanyin Zhao, Kun Zhao, Yingzhe Liu, Yue Ma, Huan Luo, Shenglan Shang, Jinyu Zhang, Fengtian He, Songtao Yu, Lixia Gan, Chunmeng Shi, Yongsheng Li, Wei Yang, Houjie Liang & Hongming Miao

Nat Commun. 2018, July; 9:2574.

Speaker: Yu-Shan Lin               Time: 16:00-16:50, Oct. 26, 2018

Commentator: Dr. Pai-Sheng Chen    Place: Room 602


Tumor-associated macrophages (TAMs) have long been known to promote cancer progression in tumor microenvironment; however, the mechanism about how lipid reprogramming contributes to macrophage polarization remains unclear. This study investigated the role of monoacylglycerol lipase (MGLL) and cannabinoid receptor 2 (CB2), of which activation always gives rise to immunosuppression, in macrophage polarization. Previous studies have reported that CB2 and its endogenous lipid-based ligands can interact with toll-like receptor 4 (TLR4), which is responsible for detecting bacteria infection, to control macrophage functions. For example, 2-arachidonoylglycerol (2-AG), which is an endogenous ligand of CB2, can directly or indirectly attenuate pro-inflammatory cytokines (IL-1b, IL-6, TNF-a) and enhance anti-inflammatory cytokines (IL-10, Arg-1, TGF-b) in lipopolysaccaride-stimulated immune cells [1]. In this study, the authors found out TAMs are short of MGLL, thereby leading to lipid accumulation and the increase of 2-AG. 2-AG will then activate CB2 and make it tangle with TLR4 to inhibit the production of pro-inflammatory cytokines, and at the same time promote the production of anti-inflammatory cytokines. Therefore, TAMs eventually impede CD8+ T cell functions and facilitate tumor progression and metastasis. In a nutshell, the findings in this study identify that the deficiency of MGLL will force macrophages to polarize from M1-like macrophage to M2-like macrophage through enhancing CB2/TLR4 interaction by decreasing 2-AG and increasing free fatty acid, thereby resulting in the promotion of defective CD8+ T cells and tumor malignancy.


  1. Kathleen L. McCoy. (2016). Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation. Mediators Inflamm, 2016:5831315.