The laboratory of Douglas Fearon is seeking an outstanding postdoc fellow for research on the interaction between the immune system and pancreatic cancer.
Our laboratory discovered that immune suppression in the tumor microenvironment of an autochthonous model of pancreatic ductal adenocarcinoma is capable of preventing cancer cell-specific CD8+ T cells from controlling tumor growth (Feig, et al, PNAS 2013). Inhibition is mediated by the interaction of the stromal cell-derived chemokine, CXCL12, with its receptor, CXCR4, on T cells prevents them from accumulating in the tumor. We are studying three aspects of this problem: how CXCL12 associates with cancer cells to protect them from immune attack; how this CXCL12 stimulates CXCR4 on T cells to suppress their influx into tumors; and the identification of new CXCR4 antagonists that will overcome this suppressive effect of CXCR4.
We have also developed a new model of pancreatic cancer metastases that has uncovered a remarkable effect of adaptive immunity in establishing occult metastases, the major clinical problem that accounts for the high rate of cancer recurrence following apparently curative surgery. We are testing the possibility that the metabolic changes that accompany pancreatic cancer may lead to activation of these dormant metastatic lesions (Flint, et al. Cell Metab 2016).