Local Release of TGF-β Inhibitor Modulates Tumor-Associated Neutrophils and Enhances Pancreatic Cancer Response to Combined Irreversible Electroporation and Immunotherapy.

ABSTRACT: Pancreatic cancer is a deadly disease with little response to standard therapies. Irreversible electroporation (IRE) has emerged as a novel ablative technique for the clinical treatment of pancreatic cancer. Combinations of IRE and immunotherapies, including anti-programmed death 1 (αPD1) immune checkpoint blockade, have shown promising efficacy in both preclinical and clinical studies. However, tumor recurrence remains an obstacle that needs to be overcome. It herein is shown that IRE induces a substantial infiltration of neutrophils into pancreatic tumors. These neutrophils are then polarized into a protumor phenotype by immunosuppressive cues, in particular transforming growth factor β (TGF-β). Using glutathione-responsive degradable mesoporous silica nanoparticles loaded with SB525334,

SUBMITTER: Peng H 

PROVIDER: S-EPMC8981446 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature