Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance

Publication date: 11 July 2016
Source:Cancer Cell, Volume 30, Issue 1
Author(s): Federico Pietrocola, Jonathan Pol, Erika Vacchelli, Shuan Rao, David P. Enot, Elisa E. Baracco, Sarah Levesque, Francesca Castoldi, Nicolas Jacquelot, Takahiro Yamazaki, Laura Senovilla, Guillermo Marino, Fernando Aranda, Sylvère Durand, Valentina Sica, Alexis Chery, Sylvie Lachkar, Verena Sigl, Norma Bloy, Aitziber Buque, Simonetta Falzoni, Bernhard Ryffel, Lionel Apetoh, Francesco Di Virgilio, Frank Madeo, Maria Chiara Maiuri, Laurence Zitvogel, Beth Levine, Josef M. Penninger, Guido Kroemer
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.

Teaser

Pietrocola et al. show that short-term fasting or autophagy-inducing caloric restriction mimetics, such as hydroxycitrate and spermidine, improves the antitumor efficacy of chemotherapy in vivo. The effect is specific for autophagy-competent tumors and depends on regulatory T cell depletion from the tumor bed.


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