Pancreatic cancer is one of the deadliest cancers, with a 5 year survival rate of 13%. The exceptionally poor prognosis of this disease can be traced to several factors. Located in a vital region of the body, the majority of primary pancreatic tumors are inoperable due to invasion of the surrounding vasculature. The disease is rapidly metastatic, with most patients presenting with metastases upon initial diagnosis. Finally, pancreatic cancers are dense, fibrotic masses that preclude adequate drug delivery.
    
Immunotherapy has shown impressive clinical benefit, particularly for metastatic melanoma. The FDA has approved three immune-modulating drugs that target activation inhibitors on T cells, ipilimumab (anti-CTLA-4) and nivolumab/pembrolizumab (anti-PD-1). Since immunotherapy targets the immune system, and not a particular type of cancer, these new drugs were originally hoped to be applicable across all tumor types as a pan-cancer medication. Indeed, significant clinical results have been seen for ipilimumab and PD-1 blockade in lung, renal, prostate, and multiple cancer types deficient in mismatch repair. However, pancreatic cancer was among the cancer types in which ipilimumab and nivolumab have largely failed.
          
​Why has pancreatic cancer been so refractory to immunotherapy? In part, we do not fully understand how tumor-specific T cells infiltrate densely fibrotic pancreatic tumors, or how to recruit more activated T cells to the tumor mass. The Dougan lab is developing novel strategies to address this question.

See manuscripts in Clinical Cancer Research(2024), Science Advances(2023),Gastroenterology(2023),Journal of Experimental Medicine(2023).