Abstract
Advances in gene engineering technology have led to the increasing clinical application of oncolytic adenovirus-targeted cancer therapy. Previous studies have demonstrated that oncolytic adenoviruses carrying decorin exhibit significant efficacy in inhibiting the growth of solid tumors. Additionally, these viruses have been shown to participate in the assembly of the tumor extracellular matrix (ECM) by expressing decorin in a subcutaneous renal cell carcinoma tumor model, thereby improving the tumor immune microenvironment. Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths worldwide, characterized by its insidious onset, limited treatment options, and poor long-term survival rates. The matrix surrounding pancreatic tumors is believed to be a key mediator of disease progression through its direct effects on cancer cells and indirect effects on the tumor immune microenvironment. In this study, we constructed a subcutaneous tumor model of pancreatic cancer and applied a combination of Decorin-carrying oncolytic adenoviruses and chemotherapy for in vivo and in vitro experiments. The results showed that the combination of the two further enhanced tumor-killing effects. In vivo experiments further confirmed that OAV-Decorin can promote IFN-γ expression, suppress TGF-β expression, improve the tumor-suppressive microenvironment, and ultimately achieve an antitumor effect.