“Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Cancer Patients”, Claudio Vernieri, Giovanni Fuca, Francesca Ligorio, Veronica Huber, Andrea Vingiani, Fabio Iannelli, Alessandra Raimondi, Darawan Rinchai, Gianmaria Frige, 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 Paolo Colombo, Saverio Minucci, Marco Foiani, Valter Daniel Longo, Giovanni Apolone, Valter Torri, Giancarlo Pruneri, Davide Bedognetti, Licia Rivoltini, Filippo de Braud2021-10-22 (fasting; similar)⁠:

In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMDs) 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, 5-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 T-helper 1/cytotoxic responses and an enrichment of interferon-gamma and other immune signatures associated with better clinical outcomes in cancer patients.

Our findings lay the foundations for phase II/III clinical trials aimed at investigating FMD antitumor efficacy in combination with standard antineoplastic treatments.

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