Immunotherapy in pancreatic adenocarcinoma—overcoming barriers to response

Pancreatic adenocarcinoma (PAC) remains one of the leading causes of cancer-related death. Despite multiple advances in targeted and immune therapies, the 5-year survival in advanced PAC remains poor. In this review, we discuss some of the unique aspects of the tumor microenvironment (TME) in PAC that may contribute to its resistance to immune therapies, as well as opportunities to potentially overcome some of these inherent barriers. Furthermore, we discuss strategies to enable immune therapies in PAC such as cytotoxic chemotherapy and radiation therapy, cancer vaccines, cytokine based therapy, oncolytic viruses, and adoptive T-cell therapy. Finally, we address a variety of targeted therapies as a strategy to further amplify immune responses in PAC.