Intermittent fasting boosts antitumor immunity by restricting CD11b+Ly6Clow Ly6Glow cell viability through glucose metabolism in murine breast tumor model

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外文摘要：Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R+and granzyme B+T cells in the tumor microenvironment.Interestingly,we observed that Ly6Glow G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocyte-monocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6Glow G-MDSC,but not Ly6Ghigh subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3+T cells,providing potential solutions for enhancing immune-based cancer interventions.

外文关键词：

Intermittent fastingLy6Glow myeloid-derived suppressor cell apoptosisExtramedullary hematopoiesisColony stimulating factorGlucose metabolism restriction

作者：

Chenghao Fu、Zhehao Liang、Zemiao Niu、Ning Chen、Yuemin Li、Zhenhua Liang、Yanwei Huo、Hao Xi、Rong Wang、Yonghuan Yan、Xiaoruo Gan、Mengtian Wang、Yun Huang、Yan Zhang、Mingming Gao、Pin Lü

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作者单位：

Postdoctoral Station for Basic Medicine,Cardiovascular Medical Science Center,Department of Cell Biology,Key Laboratory of Neural and Vascular Biology of Ministry of Education,Hebei Medical University,Shijiazhuang 050017,China

Hebei Key Laboratory of Forensic Medicine,College of Forensic Medicine,Hebei Medical University,Shijiazhuang 050017,China

Hebei Food Safety Key Laboratory,Hebei Food Inspection and Research Institute,Shijiazhuang 050091,China

Laboratory of Lipid Metabolism,Department of Biochemistry and Molecular Biology,Key Laboratory of Medical Biotechnology of Hebei Province,Shijiazhuang 050017,China

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基金：

Postdoctoral Research Funds of Hebei Medical University国家自然科学基金河北省自然科学基金National Key Research Project of Hebei ProvincePostdoctoral Research Project of Hebei ProvinceScience and Technology Research Program of Hebei Provincial CollegesHebei Provincial Key Laboratory of Nutrition and Health

项目编号：

30705010016-375932272328B202232100120375502DB2022003031QN20232292023YDYY-KF05

出版年：

2024

DOI：

10.26599/FSHW.2022.9250194

食品科学与人类健康(英文)

CSTPCD

ISSN：

年,卷(期)：2024.13(4)

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