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.

Department of Internal Medicine Center for Autophagy Research Howard Hughes Medical Institute University of Texas Southwestern Medical Center Dallas TX 73590 USA

Department of Morphology Surgery and Experimental Medicine University of Ferrara 44121 Ferrara Italy

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

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 5 Sorbonne Paris Cité 75006 Paris France

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 5 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

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

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

Gustave Roussy Cancer Campus 94800 Villejuif France; Metabolomics and Cell Biology Platforms Gustave Roussy Cancer Campus 94800 Villejuif France

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 1428 94800 Villejuif France

INSERM U866 21078 Dijon France; Faculté de Médecine Université de Bourgogne 21078 Dijon France; Centre Georges François Leclerc 21000 Dijon France

Institute for Molecular Biotechnology of the Austrian Academy of Sciences 1030 Vienna Austria

Institute of Molecular Biosciences NAWI Graz University of Graz Humboldtstraße 50 8010 Graz Austria; BioTechMed Graz Humboldtstraße 50 8010 Graz Austria

UMR7355 CNRS and University 45067 Orléans France; Institute of Infectious Disease and Molecular Medicine University of Cape Town 7925 Cape Town South Africa

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Cancer Cell. 2016 Jul 11;30(1):13-15. doi: 10.1016/j.ccell.2016.06.019. PubMed

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