Enhancing chemotherapy efficacy in pten-deficient prostate tumors by activating the senescence-associated antitumor immunity
Articolo
Data di Pubblicazione:
2014
Citazione:
Enhancing chemotherapy efficacy in pten-deficient prostate tumors by activating the senescence-associated antitumor immunity / A. Toso, A. Revandkar, D. Dimitri, I. Guccini, M. Proietti, M. Sarti, S. Pinton, J. Zhang, M. Kalathur, G. Civenni, D. Jarrossay, E. Montani, C. Marini, R. Garcia Escudero, E. Scanziani, F.M. Grassi, P. Pandolfi, C.V. Catapano, A. Alimonti. - In: CELL REPORTS. - ISSN 2211-1247. - 9:1(2014 Oct 09), pp. 75-89. [10.1016/j.celrep.2014.08.044]
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 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Animals; Antineoplastic Agents; Cell Aging; Cytokines; Female; Gene Expression Profiling; Humans; Male; Mice; Mice, Transgenic; PTEN Phosphohydrolase; Prostatic Neoplasms; Signal Transduction; Taxoids; Tumor Microenvironment; Biochemistry, Genetics and Molecular Biology (all); Medicine (all)
Elenco autori:
A. Toso, A. Revandkar, D. Dimitri, I. Guccini, M. Proietti, M. Sarti, S. Pinton, J. Zhang, M. Kalathur, G. Civenni, D. Jarrossay, E. Montani, C. Marini, R. Garcia Escudero, E. Scanziani, F.M. Grassi, P. Pandolfi, C.V. Catapano, A. Alimonti
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