title: Activating autophagy to potentiate immunogenic chemotherapy and radiation therapy.
abstract: Autophagy is fundamental to the maintenance of intracellular homeostasis in virtually all human cells. Accordingly, defective autophagy predisposes healthy cells to undergoing malignant transformation. By contrast, malignant cells are able to harness autophagy to thrive, despite adverse microenvironmental conditions, and to resist therapeutic challenges. Thus, inhibition of autophagy has been proposed as a strategy to kill cancer cells or sensitize them to therapy; however, autophagy is also critical for optimal immune function, and mediates cell-extrinsic homeostatic effects owing to its central role in danger signalling by neoplastic cells responding to immunogenic chemotherapy and/or radiation therapy. In this Perspective, we discuss accumulating preclinical and clinical evidence in support of the all-too-often dismissed possibility that activating autophagy might be a relevant clinical objective that enables an increase in the effectiveness of immunogenic chemotherapy and/or radiation therapy.
authors.affiliation: Department of Radiation Oncology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, USA.|Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 15, rue de l'Ecole de Médecine, F-75006 Paris, France; INSERM, U1138, Université Paris Descartes; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; and at Université Pierre et Marie Curie/Paris VI, Paris, France.|Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.affiliation: Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 15, rue de l'Ecole de Médecine, F-75006 Paris, France; INSERM, U1138, Université Paris Descartes; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; and at Université Pierre et Marie Curie/Paris VI, Paris, France.|Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Bravo-San Pedro
authors.affiliation: Department of Radiation Oncology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Demaria
authors.affiliation: Department of Radiation Oncology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, USA.
authors.forename: Silvia Chiara
authors.initials: SC
authors.lastname: Formenti
authors.affiliation: Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 15, rue de l'Ecole de Médecine, F-75006 Paris, France; INSERM, U1138, Université Paris Descartes; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; and at Université Pierre et Marie Curie/Paris VI, Paris, France.|Gustave Roussy Cancer Campus, Villejuif, France.|Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France; and at the Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D001343:Autophagy / Q000276:immunology*; D002986:Clinical Trials as Topic; D005544:Forecasting; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000532:radiotherapy; D059016:Tumor Microenvironment