Anti-Tumor Immune Responses in Pancreatic Cancer

Pancreatic ductal cell adenocarcinoma is one of the most aggressive cancer types, and thus far immunotherapeutic interventions have failed to provide survival benefits.

Despite the fact that a significant fraction of pancreatic cancer patients has immune infiltration into the tumor microenvironment, current immunotherapeutic interventions, including checkpoint blockade, fail to activate an anti-tumor immune response. Previous studies in melanoma have provided evidence that tumor cell-intrinsic activation of signaling pathways (e.g. WNT/beta-catenin or PI3K activation) dominantly modulates the local immune microenvironment and impacts the response to checkpoint blockade. By analyzing both T cell-inflamed and non-T cell-inflamed pancreatic cancer patient samples we aim to understand the molecular and tumor-derived factors mediating resistance to immunotherapy. We will also assess whether the composition of immune cells within the tumor microenvironment or the somatic mutational landscape of tumor cells might be influencing local anti-tumor immune responses. The goal is to identify potential targets that may convert the local microenvironment of pancreatic cancer from immune-resistant to immune-sensitive.