title: Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice.
abstract: 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.
authors.affiliation: INSERM, U848, Villejuif, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Michaud
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martins
authors.forename: Abdul Qader
authors.initials: AQ
authors.lastname: Sukkurwala
authors.forename: Sandy
authors.initials: S
authors.lastname: Adjemian
authors.forename: Yuting
authors.initials: Y
authors.lastname: Ma
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pellegatti
authors.forename: Shensi
authors.initials: S
authors.lastname: Shen
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.forename: Marie
authors.initials: M
authors.lastname: Scoazec
authors.forename: Grégoire
authors.initials: G
authors.lastname: Mignot
authors.forename: Santiago
authors.initials: S
authors.lastname: Rello-Varona
authors.forename: Maximilien
authors.initials: M
authors.lastname: Tailler
authors.forename: Laurie
authors.initials: L
authors.lastname: Menger
authors.forename: Erika
authors.initials: E
authors.lastname: Vacchelli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.forename: Francesco
authors.initials: F
authors.lastname: di Virgilio
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D037282:Calreticulin / Q000494:pharmacology; D016923:Cell Death / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008942:Mitoxantrone / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D037282:Calreticulin; D000255:Adenosine Triphosphate; D008942:Mitoxantrone