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Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer

journal contribution
submitted on 2024-04-01, 10:57 and posted on 2024-04-02, 05:20 authored by Claudio Vernieri, Giovanni Fucà, Francesca Ligorio, Veronica Huber, Andrea Vingiani, Fabio Iannelli, Alessandra Raimondi, Darawan Rinchai, Gianmaria Frigè, Antonino Belfiore, Luca Lalli, Claudia Chiodoni, Valeria Cancila, Federica Zanardi, Arta Ajaz, Salvatore Cortellino, Viviana Vallacchi, Paola Squarcina, Agata Cova, Samantha Pesce, Paola Frati, Raghvendra Mall, Paola Antonia Corsetto, Angela Maria Rizzo, Cristina Ferraris, Secondo Folli, Marina Chiara Garassino, Giuseppe Capri, Giulia Bianchi, Mario Paolo Colombo, Saverio Minucci, Marco Foiani, Valter Daniel Longo, Giovanni Apolone, Valter Torri, Giancarlo Pruneri, Davide Bedognetti, Licia Rivoltini, Filippo de Braud

In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate the safety and biological effects of cyclic, five-day FMD in combination with standard antitumor therapies. In 101 patients, the FMD was safe, feasible, and resulted in a consistent decrease of blood glucose and growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer effects in preclinical experiments. Integrated transcriptomic and deep-phenotyping analyses revealed that FMD profoundly reshapes anticancer immunity by inducing the contraction of peripheral blood immunosuppressive myeloid and regulatory T-cell compartments, paralleled by enhanced intratumor Th1/cytotoxic responses and an enrichment of IFNγ and other immune signatures associated with better clinical outcomes in patients with cancer. Our findings lay the foundations for phase II/III clinical trials aimed at investigating FMD antitumor efficacy in combination with standard antineoplastic treatments.

Other Information

Published in: Cancer discovery
License: https://creativecommons.org/licenses/by-nc-nd/4.0/
See article on publisher's website: https://doi.org/10.1158/2159-8290.CD-21-0030

History

Language

  • English

Publisher

American Association for Cancer Research

Publication Year

  • 2022

License statement

This Item is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Institution affiliated with

  • Sidra Medicine
  • Hamad Bin Khalifa University
  • Qatar Computing Research Institute - HBKU
  • College of Health and Life Sciences - HBKU

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