Targeting the IGF-Axis Potentiates Immunotherapy for Pancreatic Ductal Adenocarcinoma Liver Metastases by Altering the Immunosuppressive Microenvironment.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, resistant to chemotherapy and associated with high incidence of liver metastases and poor prognosis. Using murine models of aggressive PDAC, we show here that in mice bearing hepatic metastases, treatment with the IGF-Trap, an inhibitor of type I insulin-like growth factor receptor (IGF-IR) signaling, profoundly altered the local, immunosuppressive tumor microenvironment in the liver, curtailing the recruitment of myeloid-derived suppressor cells, reversing innate immune cell polarization and inhibiting metastatic expansion. Significantly, we found that immunotherapy with anti-PD-1 antibodies also reduced the growth of experimental PDAC liver metastases, and this effect was enhanced when combined with IGF-Trap treat

SUBMITTER: Hashimoto M 

PROVIDER: S-EPMC8677570 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature