Presentation: 2025 ND EPSCoR Annual conference 

October 21, 2025, NDSU Memorial Union, Fargo, North Dakota

Investigating the Synergistic Effect of Vascular Normalization and Immunotherapy

Pancreatic cancer is the 11th most common cancer worldwide and accounts for 4% of cancer deaths. Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most difficult cancers to treat, partially due to its nature as a "cold tumor" with limited immune infiltration and immunosuppressive environment. PDAC is also known for its leaky and nonfunctional blood vessels due to a lack of proper pericyte coverage. Tumor vessels serve as the primary route for therapeutic drugs and immune cell trafficking; therefore, abnormal vasculature hinders the drug delivery and immune infiltration. Recent studies and our preliminary work suggest that pathological pericytes exhibit an immunosuppressive phenotype, which partially explains the lower immune cell activity. Based on this knowledge, we aim to investigate the causative relationship between pericyte phenotype and the immunosuppressive tumor microenvironment. Additionally, abnormal tumor vessels contribute to the enhanced extravasation and intravasation of cancer cells during metastasis. Therefore, we are also exploring whether these connections can be applied to metastatic sites in PDAC, such as the lung and liver. Understanding these relationships will help us determine how to use immunotherapies more effectively when combined with vascular normalization to treat tumors. With multispectral imaging technology utilizing Tyramide Signal Amplification (TSA) staining, we can examine various pericyte and immune cell markers to identify correlations between the two. We are also developing an in vitro assay system to examine the inhibitory effect of pathological pericytes on the activity of immune cells. This study will identify a novel combination treatment of vascular normalization and immunotherapy to combat this deadly disease.