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

doi:10.1016/j.ccell.2016.05.016

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 journal › Article › peer-review

382 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 language	English (US)
Pages (from-to)	147-160
Number of pages	14
Journal	Cancer Cell
Volume	30
Issue number	1
DOIs	https://doi.org/10.1016/j.ccell.2016.05.016
State	Published - Jul 11 2016

Keywords

cancer
chemotherapy
immunosurveillance
regulatory T cell

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccell.2016.05.016

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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

Pietrocola, F, Pol, J, Vacchelli, E, Rao, S, Enot, DP, Baracco, EE, 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, Buque, A, Falzoni, S, Ryffel, B, Apetoh, L, Di Virgilio, F, Madeo, F, Maiuri, MC, Zitvogel, L, Levine, B, Penninger, JM & Kroemer, G 2016, 'Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance', Cancer Cell, vol. 30, no. 1, pp. 147-160. https://doi.org/10.1016/j.ccell.2016.05.016

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title = "Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance",

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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author = "Federico Pietrocola and Jonathan Pol and Erika Vacchelli and Shuan Rao and Enot, {David P.} and Baracco, {Elisa E.} and Sarah Levesque and Francesca Castoldi and Nicolas Jacquelot and Takahiro Yamazaki and Laura Senovilla and Guillermo Marino and Fernando Aranda and Sylv{\`e}re Durand and Valentina Sica and Alexis Chery and Sylvie Lachkar and Verena Sigl and Norma Bloy and Aitziber Buque and Simonetta Falzoni and Bernhard Ryffel and Lionel Apetoh and {Di Virgilio}, Francesco and Frank Madeo and Maiuri, {Maria Chiara} and Laurence Zitvogel and Beth Levine and Penninger, {Josef M.} and Guido Kroemer",

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doi = "10.1016/j.ccell.2016.05.016",

language = "English (US)",

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AU - Vacchelli, Erika

AU - Rao, Shuan

AU - Enot, David P.

AU - Baracco, Elisa E.

AU - Levesque, Sarah

AU - Castoldi, Francesca

AU - Jacquelot, Nicolas

AU - Yamazaki, Takahiro

AU - Senovilla, Laura

AU - Marino, Guillermo

AU - Aranda, Fernando

AU - Durand, Sylvère

AU - Sica, Valentina

AU - Chery, Alexis

AU - Lachkar, Sylvie

AU - Sigl, Verena

AU - Bloy, Norma

AU - Buque, Aitziber

AU - Falzoni, Simonetta

AU - Ryffel, Bernhard

AU - Apetoh, Lionel

AU - Di Virgilio, Francesco

AU - Madeo, Frank

AU - Maiuri, Maria Chiara

AU - Zitvogel, Laurence

AU - Levine, Beth

AU - Penninger, Josef M.

AU - Kroemer, Guido

PY - 2016/7/11

Y1 - 2016/7/11

N2 - 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.

AB - 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.

KW - cancer

KW - chemotherapy

KW - immunosurveillance

KW - regulatory T cell

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Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance

Abstract

Keywords

ASJC Scopus subject areas

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