Evaluating the Roles of B cells and Antibody in Pancreatic Cancer Progression - Infiltrating pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States and it is one of the most fatal human malignancies, with an overall 5-year survival rate of less than 5%. Both response to standard-of-care and immune checkpoint therapies is poor requiring alternate strategies to induce patient-specific immune responses. In pancreatic cancer pro-tumorigenic macrophage, T regulatory cells, myeloid-derived suppressor cells, and tumor-associated fibroblasts are present within the tumor beginning at early pre-invasive stages of pancreatic cancer development. These cellular subsets inhibit T cell activation and CD8+ T cell recruitment into the tumor. Additional studies have implicated tumor infiltrating B cells as a tumor-promoting subset required for epithelial carcinoma progression enhancing tumor cell survival and contributing to chronic inflammatory cues critical to tumor progression. Our preliminary findings in mouse models of Kras-driven pancreatic cancer indicate that antibodies appear to play an important role in promotion of tumor immunity and limiting metastasis. The major goal of my current research focus is to determine requirements for antibody-driven, pancreatic tumor-specific immunity using mouse models that closely recapitulate disease progression observed in patients. Furthermore we intend to elucidate antibody-dependent and independent mechanisms that promote and inhibit cancer progression using spontaneous, orthotopic, and models that mimic metastatic disease using syngenic pancreatic ductal adenocarcinomna cell lines derived from spontaneously formed neoplasms. Ultimately the findings from these studies will be utilized to test novel and modifications to currently existing treatments to harness the therapeutic capabilities of antibody and limit the immune suppressive effects of B cells in the pancreatic tumor microenvironment with the goal of providing novel therapies capable of successful translation into the clinic. As a comparative pathologist for ARP, I also contribute pathology support to research projects bridging a wide span of research areas, including cancer, autoimmunity, mucosal and transplant immunology. These collaborations involve rodent, porcine, primate models and canine cancer patients. The goal of these collaborations is to provide comparative pathology support to investigators in their respective projects.
