Cancer Cell
Volume 30, Issue 1, 11 July 2016, Pages 147-160
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Article
Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance

https://doi.org/10.1016/j.ccell.2016.05.016Get rights and content
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Highlights

  • Short-term fasting improves anticancer chemotherapy

  • Treatment with caloric restriction mimetics (CRMs) inhibits tumor growth in vivo

  • CRMs trigger an autophagy-dependent anticancer immune response

  • CRMs deplete regulatory T Cells from tumor bed

Summary

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.

Keywords

chemotherapy
cancer
immunosurveillance
regulatory T cell

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23

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24

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