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.

Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer / C. Vernieri, G. Fuca, F. Ligorio, V. Huber, A. Vingiani, F. Iannelli, A. Raimondi, D. Rinchai, G. Frige, A. Belfiore, L. Lalli, C. Chiodoni, V. Cancila, F. Zanardi, A. Ajazi, S. Cortellino, V. Vallacchi, P. Squarcina, A. Cova, S. Pesce, P. Frati, R. Mall, P.A. Corsetto, A.M. Rizzo, C. Ferraris, S. Folli, M.C. Garassino, G. Capri, G. Bianchi, M.P. Colombo, S. Minucci, M. Foiani, V.D. Longo, G. Apolone, V. Torri, G. Pruneri, D. Bedognetti, L. Rivoltini, F. de Braud. - In: CANCER DISCOVERY. - ISSN 2159-8274. - 12:1(2022 Jan), pp. 90-107. [10.1158/2159-8290.CD-21-0030]

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

A. Vingiani;P.A. Corsetto;A.M. Rizzo;S. Minucci;M. Foiani;G. Pruneri;F. de Braud
2022

Abstract

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.
Settore MED/06 - Oncologia Medica
Settore MED/04 - Patologia Generale
Settore MED/08 - Anatomia Patologica
Settore BIO/11 - Biologia Molecolare
Settore BIO/10 - Biochimica
gen-2022
Article (author)
File in questo prodotto:
File Dimensione Formato  
90.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 8.19 MB
Formato Adobe PDF
8.19 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/907301
Citazioni
  • ???jsp.display-item.citation.pmc??? 69
  • Scopus 132
  • ???jsp.display-item.citation.isi??? 127
social impact