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Abstract
Stefano Di Biase1, 4, Changhan Lee1, 4, Sebastian Brandhorst1, Brianna Manes1, Roberta Buono1, Chia-Wei Cheng1, Mafalda Cacciottolo1, Alejandro Martin-Montalvo2, Rafael de Cabo2, Min Wei1, Todd E. Morgan1, Valter D. Longo1, 3
1 Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
2Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
3 IFOM, FIRC Institute of Molecular Oncology, Milan 20139, Italy
4 Co-first author
Corresponding author
Summary
Immune-based interventions are promising strategies to achieve long-term cancer-free survival. Fasting was previously shown to differentially sensitize tumors to chemotherapy while protecting normal cells, including hematopoietic stem and immune cells, from its toxic side effects. Here, we show that the combination of chemotherapy and a fasting-mimicking diet (FMD) increases the levels of bone marrow common lymphoid progenitor cells and cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs), leading to a major delay in breast cancer and melanoma progression. In breast tumors, this effect is partially mediated by the downregulation of the stress-responsive enzyme heme oxygenase-1 (HO-1). These data indicate that FMD cycles combined with chemotherapy can enhance T cell-dependent targeted killing of cancer cells both by stimulating the hematopoietic system and by enhancing CD8+-dependent tumor cytotoxicity.
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