6533b7d0fe1ef96bd1259bc3
RESEARCH PRODUCT
Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance
Valentina SicaFrank MadeoNorma BloyMaria Chiara MaiuriErika VacchelliErika VacchelliDavid EnotFernando ArandaFernando ArandaLaura SenovillaJonathan PolSarah LevesqueNicolas JacquelotElisa E. BaraccoLaurence ZitvogelLionel ApetohLionel ApetohGuillermo MariñoGuillermo MariñoTakahiro YamazakiFrancesca CastoldiAitziber BuquéJosef M. PenningerBernhard RyffelBernhard RyffelSimonetta FalzoniBeth LevineVerena SiglSylvère DurandSylvie LachkarFrancesco Di VirgilioAlexis CheryGuido KroemerShuan RaoFederico PietrocolaFederico Pietrocolasubject
0301 basic medicineCancer ResearchATP citrate lyaseSpermidineBariatric SurgeryimmunosurveillanceT-Lymphocytes RegulatoryAutophagy-Related Protein 5[ SDV.CAN ] Life Sciences [q-bio]/Cancerchemistry.chemical_compoundMiceregulatory T cellCitrates3. Good healthImmunogenic Cell-DeathImmunosurveillancemedicine.anatomical_structureOncologyBiochemistryDifferentiationembryonic structuresImmunogenic cell deathIn-VivoHumanRegulatory T cell[SDV.CAN]Life Sciences [q-bio]/Cancer[SDV.BC]Life Sciences [q-bio]/Cellular BiologyBiologyDietary RestrictionNOProto-Oncogene Proteins p21(ras)03 medical and health sciencesMonitoring ImmunologicIn vivoCell Line TumormedicineAutophagyAnimalsHumanscancerChemotherapyBreast-CancerCaloric Restrictioncancer; chemotherapy immunosurveillance regulatory T cellAnimal[ SDV.BC ] Life Sciences [q-bio]/Cellular Biologyregulatory T AutophagyfungiNeoplasms ExperimentalcellSpermidineMethotrexate030104 developmental biologychemistryAcetylationMutationCancer researchCitrateNeoplasm Transplantationdescription
International audience; 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-07-11 |