Blockade of Stat3 oncogene addiction induces cellular senescence and reveals a cell-nonautonomous activity suitable for cancer immunotherapy.

ABSTRACT: Stat3 is constitutively activated in several tumor types and plays an essential role in maintaining their malignant phenotype and immunosupression. To take advantage of the promising antitumor activity of Stat3 targeting, it is vital to understand the mechanism by which Stat3 regulates both cell autonomous and non-autonomous processes. Here, we demonstrated that turning off Stat3 constitutive activation in different cancer cell types induces senescence, thus revealing their Stat3 addiction. Taking advantage of the senescence-associated secretory phenotype (SASP) induced by Stat3 silencing (SASP-siStat3), we designed an immunotherapy. The administration of SASP-siStat3 immunotherapy induced a strong inhibition of triple-negative breast cancer and melanoma growth associated with activation o

SUBMITTER: De Martino M 

PROVIDER: S-EPMC6996562 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature