Toso, Alberto; Revandkar, Ajinkya; Di Mitri, Diletta; Guccini, Ilaria; Proietti, Michele; Sarti, Manuela; Pinton, Sandra; Zhang, Jiangwen; Kalathur, Madhuri; Civenni, Gianluca; Jarrossay, David; Montani, Erica; Marini, Camilla; Garcia-Escudero, Ramon; Scanziani, Eugenio; Grassi, Fabio; Pandolfi, Pier Paolo; Catapano, Carlo V; Alimonti, Andrea (2014). Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity. Cell reports, 9(1), pp. 75-89. Cell Press 10.1016/j.celrep.2014.08.044
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1-s2.0-S2211124714007207-main.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (5MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology |
UniBE Contributor: |
Marini, Camilla |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2211-1247 |
Publisher: |
Cell Press |
Language: |
English |
Submitter: |
Nathalie Ursula Becher |
Date Deposited: |
13 May 2015 09:57 |
Last Modified: |
05 Dec 2022 14:47 |
Publisher DOI: |
10.1016/j.celrep.2014.08.044 |
PubMed ID: |
25263564 |
BORIS DOI: |
10.7892/boris.68903 |
URI: |
https://boris.unibe.ch/id/eprint/68903 |
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