Why do most patients with epithelial cancers not respond to T cell checkpoint blockade?

NCI Center for Cancer Research Eminent Lecture Over the past 40 years, Dr. Fearon has made contributions to our understanding of innate immunity, B cell signal transduction, memory T cells, and, most recently, cancer immunology. During the past 10 years, Dr. Fearon has trained 15 PhD and MB/PhD students at the University of Cambridge. Former post-doctoral fellows now have faculty or staff positions at outstanding institutions such as Harvard Medical School, the NIAID, University of Cambridge, King’s College London, University of Leicester, and the University of Ryukyus. His past work with a genetically engineered mouse that enables the conditional depletion of cancer associated fibroblasts led to the identification of an essential role for this stromal cell type and one of its products, CXCL12, in immune suppression by the tumor microenvironment. The Fearon laboratory studies the interaction between cancer and the immune system. Our underlying premise is that the tumor microenvironment is immune suppressive because cancer cells elicit responses characteristic of wound healing and tissue regeneration. This approach has led to the finding that activated fibroblasts in the tumor stroma mediate immune suppression in several mouse models of cancer, including the autochthonous KPC model of pancreatic ductal adenocarcinoma. Their understanding of the basis of immune suppression is evolving, but know that it involves the production of the chemokine, CXCL12, by the fibroblastic ...
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