| Literature DB >> 27411589 |
Federico Pietrocola1, Jonathan Pol2, Erika Vacchelli1, Shuan Rao3, David P Enot4, Elisa E Baracco5, Sarah Levesque5, Francesca Castoldi6, Nicolas Jacquelot7, Takahiro Yamazaki7, Laura Senovilla2, Guillermo Marino1, Fernando Aranda1, Sylvère Durand4, Valentina Sica5, Alexis Chery4, Sylvie Lachkar5, Verena Sigl3, Norma Bloy5, Aitziber Buque5, Simonetta Falzoni8, Bernhard Ryffel9, Lionel Apetoh10, Francesco Di Virgilio8, Frank Madeo11, Maria Chiara Maiuri5, Laurence Zitvogel7, Beth Levine12, Josef M Penninger3, Guido Kroemer13.
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.Entities:
Keywords: cancer; chemotherapy; immunosurveillance; regulatory T cell
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Year: 2016 PMID： 27411589 PMCID： PMC5715805 DOI： 10.1016/j.ccell.2016.05.016
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743