2021 Grantee: Robert Eil, MD
Oregon Health & Science University
Research Project: Targeting an Unrecognized Mechanism of Immune Evasion in Pancreatic Cancer
Award: 2021 Pancreatic Cancer Action Network Career Development Award made possible by Tilynn Bontrager in memory of Polly Mast
Award Period: July 1, 2021 – June 30, 2023
Dr. Eil is an Assistant Professor of Surgery and Cellular, Developmental, & Cancer Biology at Oregon Health & Science University School of Medicine (OHSU). He is a surgeon-scientist focusing on applying immunotherapies to cancers involving the pancreas and liver. In the midst of his surgery residency at OHSU, Dr. Eil pursued a research fellowship at the Surgery Branch of the National Cancer Institute (NCI), gaining expertise in T-cell biology, tumor immunology, genetic engineering and cell transfer therapies.
During his time at the NCI, Dr. Eil identified unrecognized derangements within the tumor microenvironment that contribute to suppression of T-cell function and developed therapeutic approaches to restore T cell function based on these findings. All cancer immunotherapies rely upon the activity of T-cells.
Following completion of his clinical fellowship in surgical oncology at Memorial Sloan Kettering Cancer Center, Dr. Eil was recruited back to OHSU to establish his research group. Here, he will continue to investigate the immune microenvironment and engineering T-cells to function within the context of pancreatic cancer. His multidisciplinary expertise provides a unique perspective to reinvigorate T-cell function in pancreas cancer, ultimately improving the lives and outcomes of patients suffering from this disease.
Immunotherapies that awaken the cancer-killing potential of immune T-cells (known as immune checkpoint blockade) have yielded dramatic responses in other cancer types but haven’t been widely effective for pancreatic cancer patients to date. Tumor-specific “killer” T-cells can be found within the microenvironment of pancreatic tumors, but they are inactive and not activated by immune checkpoint blocking drugs.
One characteristic specific to tumor tissue is a high abundance of cell death. Counterintuitively, the proportion of cancer cell death is inversely related to patient outcome (i.e., patients whose cancers have a high burden of cell death are actually more likely to die from their disease). This cell death within tumors leads to an elevated concentration of potassium (K+), an element normally found inside cells, within tumor tissue. During his earlier work, Dr. Eil uncovered a previously unrecognized phenomenon whereby this increased potassium profoundly affected the anti-cancer function of T-cells. This finding was significant since the successful application of immune therapies to pancreatic cancer will require the identification and reversal of T-cell suppression within tumors beyond already defined “checkpoints.”
Through this Career Development Award project, Dr. Eil and his team aim to define the extent of immune suppression enforced by potassium released following cell death in human pancreatic cancer. They will also test otherwise unexplored treatments for pancreatic cancer based on manipulating T-cells’ ability to move ions (like potassium) in and out of the cells. Finally, they will work to clarify previously unrecognized aspects of cellular biology controlled by potassium concentrations inside of cells. Ultimately, they hope these studies will advance new immune-based approaches to treat pancreatic cancer, improving the survival and quality of life for patients.