Assistant Professor, UC San Diego
Mechanisms of granulocytic cell death and immunosuppression in pancreatic cancer
Overview
Aim: Treatment/Therapy
Pancreatic cancer is an aggressive and difficult-to-treat disease that responds poorly to current therapies. One reason for this resistance is that tumors build physical and chemical barriers that block the body’s cancer-fighting immune cells from reaching and destroying tumor cells. In particular, certain immune cells called granulocytes, which include neutrophils, are drawn into the tumor and contribute to this hostile environment. These cells can form large clusters and release sticky, web-like structures known as neutrophil extracellular traps (NETs). While NETs normally help the body fight infections, in cancer they can block immune cells, encourage inflammation, and even help cancer spread.
We are investigating how NET-forming granulocytes develop and behave inside pancreatic tumors, and whether blocking them can improve treatment response. Our preliminary studies show that a specific signal from the tumor attracts granulocytes and triggers NET formation, especially in tumors that fail to respond to immunotherapy. Blocking this signal reduces granulocyte clusters and improves immunotherapy effectiveness. We will use advanced imaging, genetic models, and analysis of patient tumor samples to uncover the signals that drive harmful NET formation and test strategies to disrupt them. Overall, this project will identify new ways to dismantle tumor defenses and make pancreatic cancer more responsive to immune-based treatments.
