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Activating autophagy to potentiate immunogenic chemotherapy and radiation therapy

Nature Reviews Clinical Oncology volume 14, pages 247–258 (2017)Cite this article

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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.

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Figure 1: Autophagic responses to cellular demands.
Figure 2: Dominance of the cell-extrinsic effects of autophagy.

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Acknowledgements

L.G., J.M.B.-S.P. and G.K. gratefully acknowledge financial support from the ANR under the frame of E-Rare-2 (the ERA-Net for Research on Rare Diseases); Cancéropôle Ile-de-France; the European Commission (ArtForce); the European Research Council (ERC); the Fondation Bettencourt Schueller; the Fondation de France; the French Agence National de la Recherche (ANR) — Projets Blancs; the French Association pour la recherche sur le cancer (ARC); the French Fondation pour la Recherche Médicale (FRM); the French Institut National du Cancer (INCa); the French Ligue contre le Cancer (équipe labellisée); the LabEx Immuno-Oncology; the Paris Alliance of Cancer Research Institutes (PACRI); the SIRIC Cancer Research and Personalized Medicine (CARPEM); the SIRIC (Sites de Recherche Intégrée sur le Cancer) Stratified Oncology Cell DNA Repair and Tumour Immune Elimination (SOCRATE); the Swiss Bridge Foundation; and the Swiss Institute for Experimental Cancer Research (ISREC). The work of S.D. is supported by the Breast Cancer Research Foundation, the Chemotherapy Foundation, and the US National Institutes of Health (grants R01 CA201246 and R01 CA198533). The work of S.C.F is supported by the Breast Cancer Research Foundation; the US Department of Defence Breast Cancer Research Program (grant W81XWH-11-1-0530); and the US National Institutes of Health (grant R01 CA161891).

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Authors and Affiliations

  1. Sandra Demaria and Silvia Chiara Formenti are at the Department of Radiation Oncology, Lorenzo Galluzzi, Weill Cornell Medical College, 1300 York Avenue, New York, New York, USA.,

    Lorenzo Galluzzi, Sandra Demaria & Silvia Chiara Formenti

  2. Lorenzo Galluzzi, José Manuel Bravo-San Pedro and Guido Kroemer are at 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; Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; and at Université Pierre et Marie Curie/Paris VI, Paris, France.,

    Lorenzo Galluzzi, José Manuel Bravo-San Pedro & Guido Kroemer

  3. INSERM, U1138, Université Paris Descartes,

    Lorenzo Galluzzi, José Manuel Bravo-San Pedro & Guido Kroemer

  4. Lorenzo Galluzzi, José Manuel Bravo-San Pedro and Guido Kroemer are at Gustave Roussy Cancer Campus, Villejuif, France.,

    Lorenzo Galluzzi, José Manuel Bravo-San Pedro & Guido Kroemer

  5. France; and at the Department of Women's and Children's Health, Guido Kroemer is at Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, Karolinska University Hospital, Stockholm, Sweden.,

    Guido Kroemer

  6. and at the Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.,

    Guido Kroemer

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  1. Lorenzo Galluzzi
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  2. José Manuel Bravo-San Pedro
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  3. Sandra Demaria
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  4. Silvia Chiara Formenti
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Contributions

L.G. and J.M.B.-S.P. researched data for this article. All authors made a substantial contribution to discussions of content, L.G. wrote the manuscript, and all authors reviewed and/or edited the manuscript before submission.

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Correspondence to Lorenzo Galluzzi.

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The authors declare no competing financial interests.

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Galluzzi, L., Bravo-San Pedro, J., Demaria, S. et al. Activating autophagy to potentiate immunogenic chemotherapy and radiation therapy. Nat Rev Clin Oncol 14, 247–258 (2017). https://doi.org/10.1038/nrclinonc.2016.183

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