Shili Xu, PhD

Overview

Pancreatic tumors demonstrate extensive changes in nutrient metabolism and profound inflammation compared to healthy pancreas tissue, with both supporting pancreatic tumor growth. However, how inflammatory factors affect nutrient metabolism in pancreatic tumor cells is not clear. Among the inflammatory factors, two major classes of interferons (IFN)s, type I and II IFNs, are particularly important in pancreatic cancer. Type I IFNs are found in chronic inflammation in many pancreatic tumors, and type II IFN is often found in pancreatic tumors treated with cancer immunotherapies. We aim to model chronic inflammation and immunotherapies in pancreatic tumors in laboratory experiments by culturing pancreatic cancer cells with type I and II IFNs, respectively. Nicotinamide adenine dinucleotidie (NAD) is an essential metabolite for cancer cell proliferation and survival. Our previous research showed that the presence of IFNs lowers NAD levels, changes how pancreatic cancer cells synthesize NAD, and also increases their sensitivity to drugs that even further decrease NAD levels. We hypothesize that these specific changes in NAD metabolism in pancreatic cancer, with chronic inflammation and/or with immunotherapies, provide potential therapeutic opportunities. In our proposed study, we will comprehensively test our hypothesis in cell culture and animal models of pancreatic cancer with chronic inflammation and with immunotherapies, using clinically safe agents to decrease NAD levels in pancreatic cancer cells. If successful, our findings will be applicable for clinical treatment of subsets of pancreatic cancers with chronic inflammation and/or with immunotherapies.