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.

b INSERM U1138 Paris France

c Equipe 11 labellisée par la Ligue Nationale contre le Cancer Centre de Recherche des Cordeliers Paris France

e Université Pierre and Marie Curie Paris France

f Université Paris Sud Paris XI Faculté de Médecine Kremlin Bicêtre France

g Sotio a c Prague Czech Republic

Gustave Roussy Cancer Campus Villejuif France

h BioTechMed Graz Graz Austria

i BioTechMed Graz Graz Austria

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

Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France

Punctum to: Pietrocola F, et al. Caloric restriction mimetics reinforce anticancer immunosurveillance. Cancer Cell [in press]http://dx.doi.org/10.1016/j.ccell.2016.05.016†These authors share co-authorship. PubMed

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