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

2021; American Association for Cancer Research; Volume: 12; Issue: 1 Linguagem: Inglês

10.1158/2159-8290.cd-21-0030

2159-8290

Claudio Vernieri, Giovanni Fucá, 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 Ajazi, 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 P. Colombo, Saverio Minucci, Marco Foiani, Valter D. Longo, Giovanni Apolone, Valter Torri, Giancarlo Pruneri, Davide Bedognetti, Licia Rivoltini, Filippo de Braud,

Cancer, Stress, Anesthesia, and Immune Response

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. SIGNIFICANCE: Cyclic FMD is well tolerated and causes remarkable systemic metabolic changes in patients with different tumor types and treated with concomitant antitumor therapies. In addition, the FMD reshapes systemic and intratumor immunity, finally activating several antitumor immune programs. Phase II/III clinical trials are needed to investigate FMD antitumor activity/efficacy.This article is highlighted in the In This Issue feature, p. 1.