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研究揭示脂肪酸氧化对肥胖相关乳腺癌的影响
作者:小柯机器人 发布时间:2019/11/22 20:42:43

美国希望之城综合癌症中心Hua Yu、Saul Priceman、Chunyan Zhang等研究人员合作发现,STAT3激活诱导的CD8阳性T效应细胞脂肪酸氧化对肥胖促进的乳腺癌生长至关重要。 2019年11月21日,国际知名学术期刊《细胞—代谢》在线发表了这一成果

研究人员发现,由CD8阳性T效应细胞中激活的STAT3驱动的脂肪酸氧化(FAO)增加对于肥胖相关的乳腺癌进展至关重要。自发性乳腺癌的肥胖小鼠中的T细胞Stat敲除或用FAO抑制剂治疗会降低FAO,增加糖酵解和CD8阳性T效应细胞功能,从而抑制乳腺癌的发展。

此外,CD8阳性T细胞中的PD-1结合可激活STAT3以增加FAO,从而抑制CD8阳性T效应细胞的糖酵解和功能。

最后,富含乳腺脂肪细胞和脂肪组织的瘦素通过激活STAT3-FAO和抑制糖酵解,下调CD8阳性T细胞效应子的功能。研究人员发现,由瘦素和PD-1通过STAT3驱动的脂肪酸氧化增加在抑制CD8阳性T效应细胞糖酵解和促进肥胖相关的乳腺癌发生中起关键作用。

据了解,尽管已知肥胖对于癌症的发展至关重要,但是肥胖如何负面影响抗肿瘤免疫反应仍然未知。

附:英文原文

Title: STAT3 Activation-Induced Fatty Acid Oxidation in CD8+ T Effector Cells Is Critical for Obesity-Promoted Breast Tumor Growth

Author: Chunyan Zhang, Chanyu Yue, Andreas Herrmann, Jieun Song, Colt Egelston, Tianyi Wang, Zhifang Zhang, Wenzhao Li, Heehyoung Lee, Maryam Aftabizadeh, Yi Jia Li, Peter P. Lee, Stephen Forman, George Somlo, Peiguo Chu, Laura Kruper, Joanne Mortimer, Dave S.B. Hoon, Wendong Huang, Saul Priceman, Hua Yu

Issue&Volume: November 21, 2019

Abstract: Although obesity is known to be critical for cancer development, how obesity negativelyimpacts antitumor immune responses remains largely unknown. Here, we show that increasedfatty acid oxidation (FAO) driven by activated STAT3 in CD8+ T effector cells is critical for obesity-associated breast tumor progression. AblatingT cell Stat3 or treatment with an FAO inhibitor in obese mice spontaneously developing breasttumor reduces FAO, increases glycolysis and CD8+ T effector cell functions, leading to inhibition of breast tumor development. Moreover,PD-1 ligation in CD8+ T cells activates STAT3 to increase FAO, inhibiting CD8+ T effector cell glycolysis and functions. Finally, leptin enriched in mammary adipocytesand fat tissues downregulates CD8+ T cell effector functions through activating STAT3-FAO and inhibiting glycolysis.We identify a critical role of increased oxidation of fatty acids driven by leptinand PD-1 through STAT3 in inhibiting CD8+ T effector cell glycolysis and in promoting obesity-associated breast tumorigenesis.

DOI: 10.1016/j.cmet.2019.10.013

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30604-7

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx