Intermittent fasting boosts antitumor immunity by restricting CD11b^(+)Ly6C^(low)Ly6G^(low) cell viability through glucose metabolism in murine breast tumor model  

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 

机构地区：[1]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 [2]Hebei Key Laboratory of Forensic Medicine,College of Forensic Medicine,Hebei Medical University,Shijiazhuang 050017,China [3]Hebei Food Safety Key Laboratory,Hebei Food Inspection and Research Institute,Shijiazhuang 050091,China [4]Laboratory of Lipid Metabolism,Department of Biochemistry and Molecular Biology,Key Laboratory of Medical Biotechnology of Hebei Province,Shijiazhuang 050017,China

出　　处：《Food Science and Human Wellness》2024年第4期2327-2345,共19页食品科学与人类健康（英文）

基　　金：supported by the Postdoctoral Research Funds of Hebei Medical University(30705010016-3759);Natural Science Foundation of China(32272328);Natural Science Foundation of Hebei Province(B2022321001);National Key Research Project of Hebei Province(20375502D);Postdoctoral Research Project of Hebei Province(B2022003031);Science and Technology Research Program of Hebei Provincial Colleges(QN2023229);Hebei Provincial Key Laboratory of Nutrition and Health(2023YDYY-KF05)。

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 Ly6G^(low)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 granulocytemonocyte 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 Ly6G^(low)G-MDSC,but not Ly6G^(high)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.

关 键 词：Intermittent fasting Ly6G^(low)myeloid-derived suppressor cell apoptosis Extramedullary hematopoiesis Colony stimulating factor Glucose metabolism restriction 

分 类 号：TS201.4[轻工技术与工程—食品科学] R737.9[轻工技术与工程—食品科学与工程]