6533b839fe1ef96bd12a6660

RESEARCH PRODUCT

Autophagy-Dependent Anticancer Immune Responses Induced by Chemotherapeutic Agents in Mice

Laurie MengerLaurie MengerLaurie MengerYuting MaShensi ShenShensi ShenShensi ShenFrancesco Di VirgilioSantiago Rello-varonaSantiago Rello-varonaSantiago Rello-varonaFrançois GhiringhelliGuido KroemerMickaël MichaudMickaël MichaudMickaël MichaudMaximilien TaillerMaximilien TaillerMaximilien TaillerOliver KeppOliver KeppOliver KeppMarie ScoazecGrégoire MignotSandy AdjemianSandy AdjemianSandy AdjemianLorenzo GalluzziLorenzo GalluzziLorenzo GalluzziPatrizia PellegattiErika VacchelliErika VacchelliErika VacchelliIsabelle MartinsIsabelle MartinsIsabelle MartinsAbdul Qader SukkurwalaAbdul Qader SukkurwalaAbdul Qader SukkurwalaLaurence Zitvogel

subject

Programmed cell deathcells cancer immunogenicity calreticulin exposure hmgb1Antineoplastic AgentsBiologyimmunogenicityNOMicechemistry.chemical_compoundAdenosine TriphosphateImmune systemCell Line TumorNeoplasmsAutophagyExtracellularAnimalsHumanscancerMice Inbred BALB CMultidisciplinaryCell DeathImmunogenicityAutophagyDendritic CellsMice Inbred C57BLhmgb1chemistryCell cultureCancer researchImmunogenic cell deathcellsMitoxantroneCalreticulinAdenosine triphosphatecalreticulin exposure

description

Antineoplastic chemotherapies are particularly efficient when they elicit immunogenic cell death, thus provoking an anticancer immune response. Here we demonstrate that autophagy, which is often disabled in cancer, is dispensable for chemotherapy-induced cell death but required for its immunogenicity. In response to chemotherapy, autophagy-competent, but not autophagy-deficient, cancers attracted dendritic cells and T lymphocytes into the tumor bed. Suppression of autophagy inhibited the release of adenosine triphosphate (ATP) from dying tumor cells. Conversely, inhibition of extracellular ATP-degrading enzymes increased pericellular ATP in autophagy-deficient tumors, reestablished the recruitment of immune cells, and restored chemotherapeutic responses but only in immunocompetent hosts. Thus, autophagy is essential for the immunogenic release of ATP from dying cells, and increased extracellular ATP concentrations improve the efficacy of antineoplastic chemotherapies when autophagy is disabled.

10.1126/science.1208347http://hdl.handle.net/11392/1581870