Immunotherapy for Pancreatic Cancer

Pancreatic cancer only comprises 3% of all cancers diagnosed in the United States, yet it has become the third-leading cause of cancer-related deaths in men and women. While cytotoxic chemotherapy has improved survival in patients with metastatic disease, five-year survival rates remain poor due to inherent resistance in pancreatic cancer to conventional therapy. Immunotherapeutic approaches designed to improve survival include vaccines and checkpoint inhibitor blockade therapies. In common with other solid tumors, the use of immune checkpoint inhibitors holds promise to revolutionize the management of pancreatic cancer. However, the tumor microenvironment of pancreatic cancer is considered an immune "desert" because of the lack of natural infiltration of effector T cells, the critical cells that respond to immune checkpoint inhibitors. Cancer vaccines express tumor-associated antigens with the aim of stimulating the immune system to recognize, process, and ultimately create antitumor responses which will target and kill tumor cells. There have been modest successes with this approach with cancer vaccines although it has been shown that vaccine therapy can efficiently prime the tumor microenvironment of pancreatic cancer with the infiltration of effector T cells. In addition, other components of the tumor microenvironment, including cancer-associated fibroblasts, macrophages, and neutrophils, are increasingly thought to play strong roles in tumor progression and represent potential targets for future drug development. Future research involving immunotherapeutics for pancreatic cancer should focus on finding the combinations of a T-cell priming agent such as a cancer vaccine, an immune checkpoint inhibitor, an agent that can make the activation of effector T cells sustainable, and ideally an agent that can overcome the immunosuppressive components in the tumor microenvironment.