title: Autophagy induction for the treatment of cancer.
abstract: Cancer can be viewed in 2 rather distinct ways, namely (i) as a cell-autonomous disease in which malignant cells have escaped control from cell-intrinsic barriers against proliferation and dissemination or (ii) as a systemic disease that involves failing immune control of aberrant cells. Since macroautophagy/autophagy generally increases the fitness of cells as well as their resistance against endogenous or iatrogenic (i.e., relating to illness due to medical intervention) stress, it has been widely proposed that inhibition of autophagy would constitute a valid strategy for sensitizing cancer cells to chemotherapy or radiotherapy. Colliding with this cell-autonomous vision, however, we found that immunosurveillance against transplantable, carcinogen-induced or genetically engineered cancers can be improved by pharmacologically inducing autophagy with caloric restriction mimetics. This positive effect depends on autophagy induction in cancer cells and is mediated by alterations in extracellular ATP metabolism, namely increased release of immunostimulatory ATP and reduced adenosine-dependent recruitment of immunosuppressive regulatory T cells into the tumor bed. The combination of autophagy inducers and chemotherapeutic agents is particularly efficient in reducing cancer growth through the stimulation of CD8+T lymphocyte-dependent anticancer immune responses.
authors.affiliation: a Gustave Roussy Cancer Campus , Villejuif , France.|b INSERM , U1138 , Paris , France.|c Equipe 11 labellisée par la Ligue Nationale contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.|d Université Paris Descartes/Paris V , Sorbonne Paris Cité, Paris , France.
authors.forename: Federico
authors.initials: F
authors.lastname: Pietrocola
authors.affiliation: a Gustave Roussy Cancer Campus , Villejuif , France.|b INSERM , U1138 , Paris , France.|c Equipe 11 labellisée par la Ligue Nationale contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.|d Université Paris Descartes/Paris V , Sorbonne Paris Cité, Paris , France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pol
authors.affiliation: a Gustave Roussy Cancer Campus , Villejuif , France.|b INSERM , U1138 , Paris , France.|c Equipe 11 labellisée par la Ligue Nationale contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.|d Université Paris Descartes/Paris V , Sorbonne Paris Cité, Paris , France.|e Université Pierre & Marie Curie , Paris , France.
authors.forename: Erika
authors.initials: E
authors.lastname: Vacchelli
authors.affiliation: a Gustave Roussy Cancer Campus , Villejuif , France.|b INSERM , U1138 , Paris , France.|c Equipe 11 labellisée par la Ligue Nationale contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.|d Université Paris Descartes/Paris V , Sorbonne Paris Cité, Paris , France.|e Université Pierre & Marie Curie , Paris , France.|f Université Paris-Sud/Paris XI , Faculté de Médecine , Kremlin-Bicêtre , France.
authors.forename: Elisa E
authors.initials: EE
authors.lastname: Baracco
authors.affiliation: a Gustave Roussy Cancer Campus , Villejuif , France.|b INSERM , U1138 , Paris , France.|c Equipe 11 labellisée par la Ligue Nationale contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.|d Université Paris Descartes/Paris V , Sorbonne Paris Cité, Paris , France.|e Université Pierre & Marie Curie , Paris , France.|f Université Paris-Sud/Paris XI , Faculté de Médecine , Kremlin-Bicêtre , France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Levesque
authors.affiliation: a Gustave Roussy Cancer Campus , Villejuif , France.|b INSERM , U1138 , Paris , France.|c Equipe 11 labellisée par la Ligue Nationale contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.|d Université Paris Descartes/Paris V , Sorbonne Paris Cité, Paris , France.|e Université Pierre & Marie Curie , Paris , France.|f Université Paris-Sud/Paris XI , Faculté de Médecine , Kremlin-Bicêtre , France.|g Sotio a.c. , Prague , Czech Republic.
authors.forename: Francesca
authors.initials: F
authors.lastname: Castoldi
authors.affiliation: a Gustave Roussy Cancer Campus , Villejuif , France.|b INSERM , U1138 , Paris , France.|c Equipe 11 labellisée par la Ligue Nationale contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.|d Université Paris Descartes/Paris V , Sorbonne Paris Cité, Paris , France.|e Université Pierre & Marie Curie , Paris , France.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Maiuri
authors.affiliation: h BioTechMed-Graz , Graz , Austria.|i BioTechMed-Graz Graz , Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.affiliation: a Gustave Roussy Cancer Campus , Villejuif , France.|b INSERM , U1138 , Paris , France.|c Equipe 11 labellisée par la Ligue Nationale contre le Cancer , Centre de Recherche des Cordeliers , Paris , France.|d Université Paris Descartes/Paris V , Sorbonne Paris Cité, Paris , France.|f Université Paris-Sud/Paris XI , Faculté de Médecine , Kremlin-Bicêtre , France.|j Metabolomics and Cell Biology Platforms , Gustave Roussy Cancer Campus , Villejuif , France.|k Pôle de Biologie , Hôpital Européen Georges Pompidou, AP-HP , Paris , France.|l Department of Women's and Children's Health , Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D006801:Humans; D007157:Immunologic Surveillance; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy*
chemical_list: D000255:Adenosine Triphosphate
keywords: acetylation; caloric restriction mimetics; hydroxycitrate; immunosurveillance; regulatory T cells; spermidine