Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity

Publication date: 11 July 2016
Source:Cancer Cell, Volume 30, Issue 1
Author(s): Stefano Di Biase, Changhan Lee, Sebastian Brandhorst, Brianna Manes, Roberta Buono, Chia-Wei Cheng, Mafalda Cacciottolo, Alejandro Martin-Montalvo, Rafael de Cabo, Min Wei, Todd E. Morgan, Valter D. Longo
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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Teaser

Di Biase et al. show that combining a fasting-mimicking diet with chemotherapy increases the levels of bone marrow common lymphoid progenitor cells and cytotoxic CD8⁺ tumor-infiltrating lymphocytes, delaying tumor progression. In breast tumors, this effect is partially mediated by downregulating HO-1.


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