Publication Date:
2011-12-17
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Michaud, Mickael -- Martins, Isabelle -- Sukkurwala, Abdul Qader -- Adjemian, Sandy -- Ma, Yuting -- Pellegatti, Patrizia -- Shen, Shensi -- Kepp, Oliver -- Scoazec, Marie -- Mignot, Gregoire -- Rello-Varona, Santiago -- Tailler, Maximilien -- Menger, Laurie -- Vacchelli, Erika -- Galluzzi, Lorenzo -- Ghiringhelli, Francois -- di Virgilio, Francesco -- Zitvogel, Laurence -- Kroemer, Guido -- New York, N.Y. -- Science. 2011 Dec 16;334(6062):1573-7. doi: 10.1126/science.1208347.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM, U848, Villejuif, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22174255" target="_blank"〉PubMed〈/a〉
Keywords:
Adenosine Triphosphate/metabolism
;
Animals
;
Antineoplastic Agents/*pharmacology/therapeutic use
;
Autophagy/drug effects/*physiology
;
Calreticulin/pharmacology
;
Cell Death/immunology
;
Cell Line, Tumor
;
Dendritic Cells/immunology
;
Humans
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Mitoxantrone/pharmacology
;
Neoplasms/drug therapy/*immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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