Challenges and Opportunities for Pancreatic Cancer Immunotherapy

Pancreatic ductal adenocarcinoma (PDA) is among the most immune-resistant tumor types. Its unique genomic landscape shaped by oncogenic drivers promotes immune suppression from the earliest stages of tumor inception to subvert adaptive T cell immunity. Single-agent immune modulators have thus far proven clinically ineffective, and multi-modal therapies targeting mechanisms of immunotherapy resistance are likely needed. Here, we review novel immunotherapy strategies currently under investigation to (1) confer antigen specificity, (2) enhance T cell effector function, and (3) neutralize immunosuppressive elements within the tumor microenvironment that may be rationally combined to untangle the web of immune resistance in PDA and other tumors.