SEARCHOTHERpreclinical research, oncology

other·preclinical research, oncology, immunology, obstetrics and gynecology, nutrition·PMC10562806

Intermittent fasting induced ketogenesis inhibits mouse epithelial ovarian cancer by promoting antitumor T cell response

iScience · 12 authors, 7 centres

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This was associated with enhanced T cell responses, including increased CD4+ and CD8+ T cell percentages and effector functions.

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This was associated with enhanced T cell responses, including increased CD4+ and CD8+ T cell percentages and effector functions. T cell depletion experiments indicated CD8+ T cells were more crucial than CD4+ T cells for the IF-mediated antitumor effect. The findings suggest IF induces ketogenesis, leading to elevated BHB levels, which reprogram T cell metabolism and enhance antitumor immunity.

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other

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preclinical research

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100% · A

ORIGINAL PAPER

PMC10562806

Intermittent fasting induced ketogenesis inhibits mouse epithelial ovarian cancer by promoting antitumor T cell response

iScience

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ABSTRACT

Summary In various cancer models, dietary interventions have been shown to inhibit tumor growth, improve anticancer drug efficacy, and enhance immunity, but no such evidence exists for epithelial ovarian cancer (EOC), the most lethal gynecologic cancer. The anticancer immune responses induced by 16-h intermittent fasting (IF) were studied in mice with EOC. IF consistently reduced metabolic growth factors and cytokines that stimulate tumor growth, creating a tumor-hostile environment. Immune profiling showed that IF dramatically alters anti-cancer immunity by increasing CD4 + and CD8 + cells, Th1 and cytotoxic responses, and metabolic fitness. β-hydroxy butyrate (BHB), a bioactive metabolite produced by IF, partially imitates its anticancer effects by inducing CD8 + effector function. In a direct comparison, IF outperformed exogenous BHB treatment in survival and anti-tumor immune response, probably due to increased ketogenesis. Thus, IF and one of its metabolic mediators BHB suppress EOC growth and sustain a potent anti-tumor T cell response. Subject areas: Biological sciences, Physiology, Immunology, Cancer

CITATION EXPORT

Mary Priyanka Udumula, Harshit Singh, Faraz Rashid et al.. Intermittent fasting induced ketogenesis inhibits mouse epithelial ovarian cancer by promoting antitumor T cell response. iScience. (2023). https://doi.org/10.1016/j.isci.2023.107839

AUTHORS

12 · 7 CENTRES

Mary Priyanka Udumula, Harshit Singh, Faraz Rashid, Laila Poisson, Nivedita Tiwari, Irina Dimitrova, Miriana Hijaz, Radhika Gogoi, Margaret Swenor, Adnan Munkarah, Shailendra Giri, Ramandeep Rattan

1Department of Women’s Health Services, Henry Ford Hospital and Henry Ford Cancer Institute, Detroit, MI, USA
2Metabolomics Core, Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA
3Department of Public Health Services and Center for Bioinformatics and Henry Ford Cancer Institute, Detroit, MI, USA
4Department of Gynecology Oncology, Barbara Ann Karmanos Cancer Institute and Wayne State University, Detroit, MI, USA
5Department of Lifestyle and Functional Medicine, Henry Ford Hospital and Henry Ford Cancer Institute, Detroit, MI, USA
6Department of Oncology, Wayne State University, Detroit, MI, USA
7Department of Ob/Gyn, Michigan State University, East Lansing, MI, USA