Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance

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 BuqueSimonetta Falzoni, Bernhard Ryffel, Lionel Apetoh, Francesco Di Virgilio, Frank Madeo, Maria Chiara Maiuri, Laurence Zitvogel, Beth Levine, Josef M. Penninger, Guido Kroemer

Research output: Contribution to journalArticle

159 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)147-160
Number of pages14
JournalCancer Cell
Volume30
Issue number1
DOIs
StatePublished - Jul 11 2016

Keywords

  • cancer
  • chemotherapy
  • immunosurveillance
  • regulatory T cell

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Pietrocola, F., Pol, J., Vacchelli, E., Rao, S., Enot, D. P., Baracco, E. E., Levesque, S., Castoldi, F., Jacquelot, N., Yamazaki, T., Senovilla, L., Marino, G., Aranda, F., Durand, S., Sica, V., Chery, A., Lachkar, S., Sigl, V., Bloy, N., ... Kroemer, G. (2016). Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. Cancer Cell, 30(1), 147-160. https://doi.org/10.1016/j.ccell.2016.05.016