Fasting mimicking diet in mice delays cancer growth and reduces immunotherapy-associated cardiovascular and systemic side effects

S. Cortellino, V. Quagliariello, G. Delfanti, O. Blaževitš, C. Chiodoni, N. Maurea, A. Mauro, F. Tatangelo, F. Pisati, A. Shmahala, S. Lazzeri, V. Spagnolo, E. Visco, C. Tripodo, G. Casorati, P. Dellabona and V. D. Longo ()
Additional contact information
S. Cortellino: IFOM, The AIRC Institute of Molecular Oncology
V. Quagliariello: Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale
G. Delfanti: IRCCS San Raffaele Scientific Institute
O. Blaževitš: IFOM, The AIRC Institute of Molecular Oncology
C. Chiodoni: Fondazione IRCCS Istituto Nazionale Tumori
N. Maurea: Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale
A. Mauro: Istituto Nazionale Tumori-IRCCS “Fondazione G. Pascale”
F. Tatangelo: Istituto Nazionale Tumori-IRCCS “Fondazione G. Pascale”
F. Pisati: Histopathology Unit, Cogentech Società Benefit srl
A. Shmahala: IFOM, The AIRC Institute of Molecular Oncology
S. Lazzeri: IFOM, The AIRC Institute of Molecular Oncology
V. Spagnolo: IFOM, The AIRC Institute of Molecular Oncology
E. Visco: IFOM, The AIRC Institute of Molecular Oncology
C. Tripodo: IFOM, The AIRC Institute of Molecular Oncology
G. Casorati: IRCCS San Raffaele Scientific Institute
P. Dellabona: IRCCS San Raffaele Scientific Institute
V. D. Longo: IFOM, The AIRC Institute of Molecular Oncology

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Immune checkpoint inhibitors cause side effects ranging from autoimmune endocrine disorders to severe cardiotoxicity. Periodic Fasting mimicking diet (FMD) cycles are emerging as promising enhancers of a wide range of cancer therapies including immunotherapy. Here, either FMD cycles alone or in combination with anti-OX40/anti-PD-L1 are much more effective than immune checkpoint inhibitors alone in delaying melanoma growth in mice. FMD cycles in combination with anti-OX40/anti-PD-L1 also show a trend for increased effects against a lung cancer model. As importantly, the cardiac fibrosis, necrosis and hypertrophy caused by immune checkpoint inhibitors are prevented/reversed by FMD treatment in both cancer models whereas immune infiltration of CD3+ and CD8+ cells in myocardial tissues and systemic and myocardial markers of oxidative stress and inflammation are reduced. These results indicate that FMD cycles in combination with immunotherapy can delay cancer growth while reducing side effects including cardiotoxicity.

Date: 2023
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DOI: 10.1038/s41467-023-41066-3

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