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Open Access

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

Chenghao Fua,#, Zhehao Lianga,#,, Zemiao Niua, Ning Chena, Yuemin Lia, Zhenhua Lianga, Yanwei Huoa, Hao Xia, Rong Wanga, Yonghuan Yanb,c, Xiaoru Ganoa, Mengtian Wangb,c, Yun Huanga,c, Yan Zhangb,c( ), Mingming Gaod( ), Pin Lüa( )
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

# These authors have contributed equally to this work.

Peer review under responsibility of Tsinghua University Press.

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Abstract

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.

Keywords

Intermittent fastingExtramedullary hematopoiesisColony stimulating factorGlucose metabolism restrictionLy6Glow myeloid-derived suppressor cell apoptosis

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Food Science and Human Wellness
Volume 13 Issue 4,
July 2024
Pages 2327-2345
DOI: 10.26599/FSHW.2022.9250194
Cite this article:
Fu C, Liang Z, Niu Z, et al. Intermittent fasting boosts antitumor immunity by restricting CD11b+Ly6Clow Ly6Glow cell viability through glucose metabolism in murine breast tumor model. Food Science and Human Wellness, 2024, 13(4): 2327-2345. https://doi.org/10.26599/FSHW.2022.9250194

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Received: 29 April 2023
Revised: 28 May 2023
Accepted: 17 June 2023
Published: 20 May 2024
© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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