Immuno-Oncology in Pancreatic Cancer

Immunotherapy is currently a rapidly growing arena representing a paradigm shift in the treatment of solid malignancies offering a novel armamentarium beyond surgical resection, conventional chemotherapy, and radiation strategies. Targeting immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 and programmed death 1/programmed death ligand 1 has had immense clinical impact resulting in sustained treatment response for a subset of patients with certain malignancies notably becoming standard of care for melanoma, non-small-cell lung cancer, renal cell cancer, head and neck carcinoma, hepatocellular cancer, and certain metastatic colorectal cancers. Unfortunately, there has been limited success in the effectiveness of immunotherapy particularly immune checkpoint blockade in the treatment of pancreatic cancer. Preclinical and clinical investigations into the complex tumour microenvironment associated with pancreatic cancer that is composed of immune, stromal cells, and extracellular matrix proteins has begun to shed light on important attributes of this microenvironment that functions as a barrier to the effectual use of immunotherapy. PDAC with its immune-privileged nature, starting from the early pre-neoplastic state, appears to escape easily from the antitumor immune response. Different mechanisms as to how cells achieve immune-privileged status have been hypothesized. Among them are decreased antigenicity and impaired immunogenicity via both cancer cell-intrinsic mechanisms and an augmented immunosuppressive TME. In this chapter, we will discuss the progress that has been made in treating pancreatic cancer with immunotherapy, the barriers that have limited treatment success, strategies to determine those patients who are more likely to respond, and finally breakthroughs with combination treatments that may hold promise for the future improved management of this disease.