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Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance

Federico Pietrocola 1, 2 Jonathan Pol 3, 1, 2 Erika Vacchelli 1, 2 Shuan Rao David p. Enot 2 Elisa e. Baracco 1, 2 Sarah Levesque 1, 2, 4 Francesca Castoldi 5 Nicolas Jacquelot 6 Takahiro Yamazaki 6 Laura Senovilla 7 Guillermo Marino Fernando Aranda 8, 1 Sylvère Durand 9, 10 Valentina Sica Alexis Chery 11 Sylvie Lachkar 12 Verena Sigl Norma Bloy 5 Aitziber Buque 1 Simonetta Falzoni Bernhard Ryffel 13 Lionel Apetoh 14, 15 Francesco Di virgilio Frank Madeo 16 Maria chiara Maiuri 17 Laurence Zitvogel 6, 15 Beth Levine Josef m. Penninger 1, 18 Guido Kroemer 19, 20, 1, 4, 21, 3, *
* Corresponding author
1 Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 - Apoptose, cancer et immunité
IGR - Institut Gustave Roussy, CRC - Centre de Recherche des Cordeliers
10 TGE Réseau National de RPE interdisciplinaire - 3443 - RENARD
LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, AMU - Aix Marseille Université, UNISTRA - Université de Strasbourg, ENSCP - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL, UPD5 - Université Paris Descartes - Paris 5 : FR 3443, FR-CNRS 3443, Université de Lille, SU - Sorbonne Université, CNRS - Centre National de la Recherche Scientifique : FR 3443
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.
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01431196
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Submitted on : Tuesday, January 10, 2017 - 3:43:53 PM
Last modification on : Thursday, July 9, 2020 - 9:21:46 AM

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Federico Pietrocola, Jonathan Pol, Erika Vacchelli, Shuan Rao, David p. Enot, et al.. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. Cancer Cell, Elsevier, 2016, 30 (1), pp.147 - 160. ⟨10.1016/j.ccell.2016.05.016⟩. ⟨hal-01431196⟩

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