title: Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.
abstract: Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed.
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France.
authors.forename: Federico
authors.initials: F
authors.lastname: Pietrocola
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pol
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Vacchelli
authors.affiliation: Institute for Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: Shuan
authors.initials: S
authors.lastname: Rao
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800 Villejuif, France.
authors.forename: David P
authors.initials: DP
authors.lastname: Enot
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris-Sud/Paris-Saclay, Faculté de Médecine, 94276 Kremlin-Bicêtre, France.
authors.forename: Elisa E
authors.initials: EE
authors.lastname: Baracco
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris-Sud/Paris-Saclay, Faculté de Médecine, 94276 Kremlin-Bicêtre, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Levesque
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris-Sud/Paris-Saclay, Faculté de Médecine, 94276 Kremlin-Bicêtre, France; Sotio a.c., 17000 Prague, Czech Republic.
authors.forename: Francesca
authors.initials: F
authors.lastname: Castoldi
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; Université Paris-Sud/Paris-Saclay, Faculté de Médecine, 94276 Kremlin-Bicêtre, France; INSERM U1015, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, 94800 Villejuif, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Jacquelot
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; Université Paris-Sud/Paris-Saclay, Faculté de Médecine, 94276 Kremlin-Bicêtre, France; INSERM U1015, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, 94800 Villejuif, France.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Senovilla
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Marino
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France.
authors.forename: Fernando
authors.initials: F
authors.lastname: Aranda
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800 Villejuif, France.
authors.forename: Sylvère
authors.initials: S
authors.lastname: Durand
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris-Sud/Paris-Saclay, Faculté de Médecine, 94276 Kremlin-Bicêtre, France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sica
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800 Villejuif, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Chery
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris-Sud/Paris-Saclay, Faculté de Médecine, 94276 Kremlin-Bicêtre, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lachkar
authors.affiliation: Institute for Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: Verena
authors.initials: V
authors.lastname: Sigl
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris-Sud/Paris-Saclay, Faculté de Médecine, 94276 Kremlin-Bicêtre, France.
authors.forename: Norma
authors.initials: N
authors.lastname: Bloy
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris-Sud/Paris-Saclay, Faculté de Médecine, 94276 Kremlin-Bicêtre, France.
authors.forename: Aitziber
authors.initials: A
authors.lastname: Buque
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Falzoni
authors.affiliation: UMR7355, CNRS and University, 45067 Orléans, France; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 7925 Cape Town, South Africa.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: INSERM, U866, 21078 Dijon, France; Faculté de Médecine, Université de Bourgogne, 21078 Dijon, France; Centre Georges François Leclerc, 21000 Dijon, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Apetoh
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Virgilio
authors.affiliation: Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, 8010 Graz, Austria; BioTechMed-Graz, Humboldtstraße 50, 8010 Graz, Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris-Sud/Paris-Saclay, Faculté de Médecine, 94276 Kremlin-Bicêtre, France.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Maiuri
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; Université Paris-Sud/Paris-Saclay, Faculté de Médecine, 94276 Kremlin-Bicêtre, France; INSERM U1015, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, 94800 Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: Department of Internal Medicine, Center for Autophagy Research, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 73590, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Levine
authors.affiliation: Institute for Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.affiliation: Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM, U1138, 75006 Paris, France; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France; Department of Women's and Children's Health, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; INSERM U1138, Centre de Recherche des Cordeliers, 75006 Paris, France. Electronic address: kroemer@orange.fr.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D001343:Autophagy; D000071187:Autophagy-Related Protein 5 / Q000235:genetics; D031204:Caloric Restriction / Q000379:methods; D045744:Cell Line, Tumor; D002951:Citrates / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D015166:Monitoring, Immunologic; D009154:Mutation; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000178:diet therapy* / Q000188:drug therapy* / Q000276:immunology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D013095:Spermidine / Q000008:administration & dosage* / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D002951:Citrates; C007999:hydroxycitric acid; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras); D013095:Spermidine; D008727:Methotrexate
keywords: cancer; chemotherapy; immunosurveillance; regulatory T cell