Role of Macrophage-Induced Inflammation in Mesothelioma
Annual rept. 1 Jul 2010-30 Jun 2011
CALIFORNIA UNIV SAN FRANCISCO
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Macrophages are a major inflammatory cell in the asbestos-induced tumor, mesothelioma, and may help maintain tumor resistance to therapy. In this second year, we have completed many tasks that confirm the importance of the macrophage in the inflammatory cell environment of mesothelioma. We can polarize macrophages to either an M1 anti-tumor or M2 pro-tumor phenotype and that M1-polarized macrophages derived from a variety of sources including human mesothelioma increase mesothelioma cell apoptosis and chemosensitivity. In our orthotopic murine mesothelioma model, the depletion of macrophages has increased the mesothelioma response to chemotherapy. We now plan to move to more clinically relevant models, using a denovo mouse mesothelioma model MexTag that closely models human mesothelioma, chemotherapy regimens used in patients with mesothelioma and a non-toxic CSF1 receptor inhibitor already in clinical trials to manipulate macrophages. In our final year, we aim to resolve important questions about the role of the macrophage and how polarization or depletion of macrophages within the tumor can sensitize the mesothelioma cell to treatment.
- Medicine and Medical Research