Pancreatic ductal adenocarcinoma is a lethal disease expected to become the second leading cause of cancer death in the United States by 2025. A major barrier to effective treatment of PDA is the extensive remodeling of the surrounding connective tissue that the cancer cells usurp to support their growth. This remodeled tissue forms a physical barrier that limits access of potentially therapeutic treatments to the cancer cells, suppresses the immune systems attempts to inhibit tumor growth, and attenuates efficacy of immunotherapies. Dr.Puré’s lab and others have identified a population of non-malignant connective tissue cells referred to as cancer-associated fibroblasts (CAFs), that expands remarkably and is activated in the context of pancreatic cancer. They have also established that this population plays a major role in promoting the development and progression, as well as therapeutic resistance, in pancreatic cancer.
In this project, Dr. Xiao will use state-of-the-art technologies to define the mechanisms by which CAFs promote pancreatic cancer, protect pancreatic cancer cells from the host’s immune system, and contribute to resistance to immunotherapy in this lethal cancer. The results of Dr. Xiao’s proposed studies will inform the development of therapeutic approaches to enhance anti-tumor immunity in pancreatic cancer patients and to render pancreatic cancer cells vulnerable to the rapidly expanding options for immunotherapy.
Projects and Grants
Impact of FAP+ stromal cell depletion on the immune landscape of pancreatic ductal adenocarcinoma
University of Pennsylvania | All Cancers | 2022 | Ellen Puré, Ph.D.
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