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Cancer Cell. 2016 Jul 11;30(1):147-160. doi: 10.1016/j.ccell.2016.05.016.

Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.

Author information

1
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.
2
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.
3
Institute for Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
4
Gustave Roussy Cancer Campus, 94800 Villejuif, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800 Villejuif, France.
5
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.
6
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.
7
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.
8
Department of Morphology, Surgery and Experimental Medicine University of Ferrara, 44121 Ferrara, Italy.
9
UMR7355, CNRS and University, 45067 Orléans, France; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 7925 Cape Town, South Africa.
10
INSERM, U866, 21078 Dijon, France; Faculté de Médecine, Université de Bourgogne, 21078 Dijon, France; Centre Georges François Leclerc, 21000 Dijon, France.
11
Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, 8010 Graz, Austria; BioTechMed-Graz, Humboldtstraße 50, 8010 Graz, Austria.
12
Department of Internal Medicine, Center for Autophagy Research, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 73590, USA.
13
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.

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.

KEYWORDS:

cancer; chemotherapy; immunosurveillance; regulatory T cell

PMID:
27411589
PMCID:
PMC5715805
DOI:
10.1016/j.ccell.2016.05.016
[Indexed for MEDLINE]
Free PMC Article

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