Pancreatic cancer, the third-leading cause of cancer-related deaths in the United States, is a highly metastatic disease that often spreads to the liver, which is known to play a role in dampening T cell activity. Cancer patients with liver metastases respond particularly poorly to checkpoint immunotherapy, for reasons that are not fully understood. Therefore, Dr. Stone aims to address this gap in our knowledge. Specifically, she believes the liver microenvironment—and the myeloid cells within it—may be playing a role in preventing these immune responses against tumors.
Previously, her team found that pancreatic cancer cells can stimulate liver cells to recruit myeloid cells and create an environment conducive to metastasis. Now, she aims to (a) define the mechanism by which activated liver cells recruit immune-suppressing myeloid cells to the liver microenvironment, and (b) determine if the immunosuppressive liver microenvironment can be reversed to enable a T cell response and sensitize pancreatic cancer to immunotherapy. Ultimately, Stone hopes her findings will provide key insights into the mechanisms regulating T cell activity in pancreatic cancer as well as potential strategies to reverse immune tolerance for therapeutic benefit.
Projects and Grants
A role for the liver microenvironment in cancer immunosurveillance
University of Pennsylvania | Pancreatic Cancer | 2019 | Gregory Beatty, M.D., Ph.D.
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