What if immune system efficacy against cancerous cells could be reinforced by a diet in which calories are not reduced but nutrients are precisely determined? This what Inserm researchers from Université Côte d’Azur, through a study of the effects of restrictive diets on tumor growth in mice, have been exploring. They have observed that a low-protein diet restricts tumor development by increasing immune response. The findings, to be published in Cell metabolism, have proved promising in understanding anti-tumor immunity in mice and pave the way for new studies in humans.
Despite the recent popularity of fasting in preventing cancer, in reinforcing chemotherapy and in extending life expectancy in patients with tumors, there is no solid scientific proof to support its efficacy at present. In reality, clinical trials are virtually non-existent in humans and the findings obtained from animal models are highly debatable. Prolonged calorie reduction can be an aggravating factor in the undernourishment and loss of muscle mass (sarcopenia) frequently associated with chemotherapy.
An Inserm team at Université Côte d’Azur decided to focus on a hypothesis by which modulating the intake of macronutrients (carbohydrates, fats and proteins) rather than that of calories, could restrict tumor growth. The researchers compared the effect of various diets, with varying levels of carbohydrates and proteins but the same number of calories, on tumor growth in mice. The results show that it was a low-protein and not a low-carbohydrate diet that had a positive impact on limiting tumor growth and prolonging life expectancy in mice.
When studying the molecular mechanisms linked to this phenomenon, the researchers observed that this strengthened immunosurveillance was linked to tumor cell secretion of immune system alert proteins, known as cytokines. According to the study, reducing proteins in the diet renders the available quantity of certain amino acids (constituents of proteins) insufficient – and these are substances to which cancer cells are highly sensitive. When access to amino acids is reduced, stress is triggered in the tumor cells, which then release cytokines and thereby activate a strong immune response against the tumor.
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Low-Protein Diet Induces IRE1α-Dependent Anticancer Immunosurveillance Camila Rubio-Patiño,1,9 Jozef P. Bossowski,1,9 Gian Marco De Donatis,1 Laura Mondragón,1 Elodie Villa,1 Lazaro E. Aira,1 Johanna Chiche,1 Rana Mhaidly,1 Cynthia Lebeaupin,1 Sandrine Marchetti,1 Konstantinos Voutetakis,2,3Aristotelis Chatziioannou,2,4 Florence A. Castelli,5 Patricia Lamourette,5 Emeline Chu-Van,5 François Fenaille,5 Tony Avril,6,7 Thierry Passeron,1 John B. Patterson,8 Els Verhoeyen,1 Béatrice Bailly-Maitre,1 Eric Chevet,6,7 and Jean-Ehrland Ricci1,10,* 1Université Côte d’Azur, INSERM U1065, C3M, 151 route de St Antoine de Ginestière, BP 23194, 06204 Nice, France 2Institute of Biology, Medicinal Chemistry and Biotechnology, NHRF, 11635 Athens, Greece 3Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece 4e-NIOS Applications PC, 17671 Kallithea-Athens, Greece 5Service de Pharmacologie et Immunoanalyse (SPI), Laboratoire d’Etude du Métabolisme des Médicaments, CEA, INRA, Université Paris Saclay, MetaboHUB, 91191 Gif-sur-Yvette, France 6Inserm U1242 «Chemistry, Oncogenesis, Stress, Signaling», Universite´ Rennes 1, 35042 Rennes, France 7Centre de Lutte Contre le Cancer Eugène Marquis, 35042 Rennes, France 8Fosun Orinove, Newbury Park, CA 91320, USA 9These authors contributed equally 10Lead Contact Cell Metabolism : doi.org/10.1016/j.cmet.2018.02.009