Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity.

Details

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State: Serval
Version: Final published version
Serval ID
serval:BIB_8411D80B9994
Type
Article: article from journal or magazin.
Collection
Publications
Title
Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity.
Journal
Cell Reports
Author(s)
Toso A., Revandkar A., Di Mitri D., Guccini I., Proietti M., Sarti M., Pinton S., Zhang J., Kalathur M., Civenni G., Jarrossay D., Montani E., Marini C., Garcia-Escudero R., Scanziani E., Grassi F., Pandolfi P.P., Catapano C.V., Alimonti A.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
9
Number
1
Pages
75-89
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Prosenescence therapy has recently emerged as a novel therapeutic approach for treating cancer. However, this concept is challenged by conflicting evidence showing that the senescence-associated secretory phenotype (SASP) of senescent tumor cells can have pro- as well as antitumorigenic effects. Herein, we report that, in Pten-null senescent tumors, activation of the Jak2/Stat3 pathway establishes an immunosuppressive tumor microenvironment that contributes to tumor growth and chemoresistance. Activation of the Jak2/Stat3 pathway in Pten-null tumors is sustained by the downregulation of the protein tyrosine phosphatase PTPN11/SHP2, providing evidence for the existence of a novel PTEN/SHP2 axis. Importantly, treatment with docetaxel in combination with a JAK2 inhibitor reprograms the SASP and improves the efficacy of docetaxel-induced senescence by triggering a strong antitumor immune response in Pten-null tumors. Altogether, these data demonstrate that immune surveillance of senescent tumor cells can be suppressed in specific genetic backgrounds but also evoked by pharmacological treatments.
Keywords
Animals, Antineoplastic Agents/pharmacology, Cell Aging/immunology, Cytokines/immunology, Female, Gene Expression Profiling, Humans, Male, Mice, Mice, Transgenic, PTEN Phosphohydrolase/deficiency, PTEN Phosphohydrolase/immunology, Prostatic Neoplasms/drug therapy, Prostatic Neoplasms/genetics, Signal Transduction, Taxoids/pharmacology, Tumor Microenvironment
Pubmed
Web of science
Open Access
Yes
Create date
18/10/2016 16:03
Last modification date
08/05/2019 21:18
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