Andrea Alimonti
Oncology Institute of Southern Switzerland (IOSI), Switzerland
Title: Enhancing Chemotherapy Efficacy in Pten-Deficient Prostate Tumors by Activating the Senescence-Associated Antitumor Immunity
Biography
Biography: Andrea Alimonti
Abstract
Pro-senescence 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 anti tumorigenic effects. Here in, 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 chemo resistance. Activation of the Jak2/Stat3 pathway in Pten-null tumors is sustained by the down regulation 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. Herethe author will discuss how immune surveillance of senescent tumor cells can be suppressed in specific genetic backgrounds but also evoked by pharmacological treatments. Finally the author will provide evidence that novel immunotherapies can be used in combination with chemotherapy to enhance the anti-tumor response in the treatment of prostate cancer