Scientific publications

Caloric Restriction Mimetics enhance anticancer Immunity

Jun 11, 2016 | Magazine: Cancer Cell

Federico Pietrocola 1, Jonathan Pol 2, Erika Vacchelli 1, Shuan Rao 3, David P Enot 4, Elisa E Baracco 5, Sarah Levesque 5, Francesca Castoldi 6, Nicolas Jacquelot 7, Takahiro Yamazaki 7, Laura Senovilla 2, Guillermo Marino 1, Fernando Aranda 1, Sylvère Durand 4, Valentina Sica 5, Alexis Chery 4, Sylvie Lachkar 5, Verena Sigl 3, Norma Bloy 5, Aitziber Buque 5, Simonetta Falzoni 8, Bernhard Ryffel 9, Lionel Apetoh 10, Francesco Di Virgilio 8, Frank Madeo 11, Maria Chiara Maiuri 5, Laurence Zitvogel 7, Beth Levine 12, Josef M Penninger 3, Guido Kroemer 13


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.

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