Role of Macrophage-induced Inflammation in Mesothelioma
Final rept. 1 Jul 2009-30 Jun 2012
CALIFORNIA UNIV SAN FRANCISCO
Pagination or Media Count:
Macrophages are a major inflammatory cell in malignant pleural mesothelioma and may help maintain tumor resistance to therapy. In this final year, we have completed the key tasks that confirm the importance of the macrophage in the inflammatory cell environment of mesothelioma. We have confirmed that it is possible to alter the polarization of macrophages to either an M1 anti-tumor or M2 pro-tumor phenotype and that a shift toward the Th1 phenotype or depletion of macrophages increases mesothelioma cell apoptosis and chemosensitivity. In our orthotopic murine mesothelioma model, the depletion of macrophages increases the mesothelioma response to chemotherapy. We have recently used a non-toxic CSF1 receptor inhibitor already in clinical trials to manipulate macrophages and shown that the tumors become more responsive to chemotherapy regimens used in patients with mesothelioma. At the end of our three year award, we have convincing evidence that manipulation of macrophages can alter the response of mesothelioma to standard therapy. Our major publications on these findings are in preparation and an RO1 application with a clinical trial included is planned for submission this fall.
- Medicine and Medical Research