title: Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity.
abstract: 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.
authors.affiliation: Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Biase
authors.affiliation: Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Changhan
authors.initials: C
authors.lastname: Lee
authors.affiliation: Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandhorst
authors.affiliation: Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Brianna
authors.initials: B
authors.lastname: Manes
authors.affiliation: Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Roberta
authors.initials: R
authors.lastname: Buono
authors.affiliation: Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Cheng
authors.affiliation: Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Cacciottolo
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martin-Montalvo
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.affiliation: Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.affiliation: Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Morgan
authors.affiliation: Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.|IFOM, FIRC Institute of Molecular Oncology, Milano, Italy.
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000178:diet therapy* / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D018450:Disease Progression; D015536:Down-Regulation; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D005215:Fasting; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology*; D061986:MCF-7 Cells; D051379:Mice; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
chemical_list: D004317:Doxorubicin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1