title: An autophagy-dependent anticancer immune response determines the efficacy of melanoma chemotherapy.
abstract: There is ample experimental and clinical evidence that chemotherapies are more efficient if they succeed in (re)activating immune surveillance, hence triggering a long-term immune response against residual tumor cells. Most of the preclinical evidence supporting this notion has been obtained with transplantable cancers, for which it has been shown that chemotherapy-induced autophagy in cancer cells is mandatory for the recruitment of myeloid cells into the tumor bed and the subsequent T lymphocyte-mediated reduction in tumor growth. Here, we characterized the chemotherapeutic response of melanomas caused by 4-hydroxy-tamoxifen-induced expression of the Cre recombinase in melanocytes that results in the activation of oncogenicBraftogether with the inactivation of the tumor suppressorPten, as well as the optional inactivation of the essential autophagy geneAtg7. Systemic chemotherapy with the anthracycline Mitoxantrone (MTX) reduced the growth of autophagy-competent melanomas (genotype:BrafCa/+;Ptenfl/fl;Atg7+/+), yet failed to affect the progression of autophagy-deficient melanomas (genotype:BrafCa/+;Ptenfl/fl;Atg7fl/fl). The growth-inhibitory effect of MTX on autophagy-competent melanomas was abolished by the combined depletion of CD4+or CD8+T lymphocytes. In conclusion, it appears that the success of chemotherapy against "spontaneous," genetically induced cancers is governed by the same rules as those applicable to transplantable tumors.
authors.affiliation: Equipe 11 labellisée par la Ligue Nationale contre le cancer; INSERM U1138; Centre de Recherche des Cordeliers ; Paris, France ; Metabolomics and Molecular Cell Biology platforms; Gustave Roussy Comprehensive Cancer Center ; Villejuif, France ; Université Paris Descartes; Sorbonne Paris Cité ; Paris, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Michaud
authors.affiliation: Rutgers Cancer Institute of New Jersey ; New Brunswick, NJ USA.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Xie
authors.affiliation: Equipe 11 labellisée par la Ligue Nationale contre le cancer; INSERM U1138; Centre de Recherche des Cordeliers ; Paris, France ; Metabolomics and Molecular Cell Biology platforms; Gustave Roussy Comprehensive Cancer Center ; Villejuif, France ; Université Paris Descartes; Sorbonne Paris Cité ; Paris, France.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Bravo-San Pedro
authors.affiliation: INSERM U1015 ; Villejuif, France ; Université Paris Sud-XI; Faculté de Médecine ; Le Kremlin Bicêtre, France ; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) ; Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: Rutgers Cancer Institute of New Jersey ; New Brunswick, NJ USA ; Department of Molecular Biology and Biochemistry; Rutgers University ; Piscataway, NJ USA ; University of Medicine and Dentistry of New Jersey; Robert Wood Johnson Medical School ; Piscataway, NJ USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: White
authors.affiliation: Equipe 11 labellisée par la Ligue Nationale contre le cancer; INSERM U1138; Centre de Recherche des Cordeliers ; Paris, France ; Metabolomics and Molecular Cell Biology platforms; Gustave Roussy Comprehensive Cancer Center ; Villejuif, France ; Université Paris Descartes; Sorbonne Paris Cité ; Paris, France ; Pôle de Biologie; Hôpital Européen Georges Pompidou ; Paris, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
keywords: anthracycline; autophagy; cancer