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 2014-10-09 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. application/pdf https://localhost:5000/ark:/12658/srd1319092 https://susi.usi.ch/global/documents/319092 https://susi.usi.ch/documents/319092/files/Toso_CR_2014.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2014.08.044 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319092 info:eu-repo/semantics/openAccess CC BY-NC-ND Cell reports. - 2014, vol. 9, no. 1, p. 75-89 info:eu-repo/classification/udc/61 Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity http://purl.org/coar/resource_type/c_6501