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Article: Enhancing chemotherapy efficacy in pten-deficient prostate tumors by activating the senescence-associated antitumor immunity

TitleEnhancing chemotherapy efficacy in pten-deficient prostate tumors by activating the senescence-associated antitumor immunity
Authors
KeywordsAnimals
Antineoplastic Agents/*pharmacology
Cell Aging/immunology
Cytokines/immunology
Female
Gene Expression Profiling
Humans
Male
Mice
Mice, Transgenic
PTEN Phosphohydrolase/*deficiency/*immunology
Issue Date2014
PublisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports
Citation
Cell Reports, 2014, v. 9 n. 1, p. 75-89 How to Cite?
AbstractProsenescence 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 theprotein 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.
Persistent Identifierhttp://hdl.handle.net/10722/219920
ISSN
2015 Impact Factor: 7.87
2015 SCImago Journal Rankings: 8.588
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorToso, A-
dc.contributor.authorRevandkar, A-
dc.contributor.authorDi Mitri, D-
dc.contributor.authorGuccini, I-
dc.contributor.authorProietti, M-
dc.contributor.authorSarti, M-
dc.contributor.authorPinton, S-
dc.contributor.authorZhang, J-
dc.contributor.authorKalathur, M-
dc.contributor.authorCivenni, G-
dc.contributor.authorJarrossay, D-
dc.contributor.authorMontani, E-
dc.contributor.authorMarini, C-
dc.contributor.authorGarcia-Escudero, R-
dc.contributor.authorScanziani, E-
dc.contributor.authorGrassi, F-
dc.contributor.authorPandolfi, PP-
dc.contributor.authorCatapano, CV-
dc.contributor.authorAlimonti, A-
dc.date.accessioned2015-10-02T09:21:47Z-
dc.date.available2015-10-02T09:21:47Z-
dc.date.issued2014-
dc.identifier.citationCell Reports, 2014, v. 9 n. 1, p. 75-89-
dc.identifier.issn2211-1247-
dc.identifier.urihttp://hdl.handle.net/10722/219920-
dc.description.abstractProsenescence 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 theprotein 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.-
dc.languageeng-
dc.publisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports-
dc.relation.ispartofCell Reports-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectAnimals-
dc.subjectAntineoplastic Agents/*pharmacology-
dc.subjectCell Aging/immunology-
dc.subjectCytokines/immunology-
dc.subjectFemale-
dc.subjectGene Expression Profiling-
dc.subjectHumans-
dc.subjectMale-
dc.subjectMice-
dc.subjectMice, Transgenic-
dc.subjectPTEN Phosphohydrolase/*deficiency/*immunology-
dc.titleEnhancing chemotherapy efficacy in pten-deficient prostate tumors by activating the senescence-associated antitumor immunity-
dc.typeArticle-
dc.identifier.emailZhang, J: jzhang1@hku.hk-
dc.identifier.authorityZhang, J=rp01713-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.celrep.2014.08.044-
dc.identifier.pmid25263564-
dc.identifier.scopuseid_2-s2.0-84907998102-
dc.identifier.volume9-
dc.identifier.issue1-
dc.identifier.spage75-
dc.identifier.epage89-
dc.identifier.isiWOS:000344468100009-
dc.publisher.placeUnited States-

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