Macrophages as a Factor Effecting Survival for Persons with Mesothelioma
Almost every asbestos lawyer learns something about macrophages trying – but failing – to engulf asbestos fibers. New research findings indicate macrophages also may become a target for doctors trying to prolong life for persons suffering from mesothelioma. Set out below is the abstract from a poster presented at AACR’s spring 2013 meeting.
"We, and others, have previously reported that macrophages infiltrating mammary adenocarcinomas foster late-stage cancer progression1-3, and that targeted therapies diminishing macrophage presence in tumors, and improve response to standard chemotherapy (CTX) resulting in slowed primary tumor growth, reduced pulmonary metastasis and increased overall survival (OS) of tumor-bearing mice4,5. These experimental studies correlate with clinical findings indicating that high densities of CD68+ myeloid cells correlate with reduced OS in patients with breast cancer6. Malignant mesotheliomas (MM), a rare cancer that can develop as a result of prior asbestos exposure, is highly resistant to conventional cytotoxic therapy7, and in the pleural space is associated with significant densities of macrophages that also correlate with decreased OS8. To investigate a functional role for macrophages in fostering neoplastic progression of MM, and/or in limiting response to CTX, we investigated the efficacy of several antagonists targeting the colony stimulating factor-1 (CSF1)/CSF-1 receptor (CSF1-R) CSF-1R signaling cascade to reveal the functional significance of macrophages in MM, and to determine if this class of agents exhibited efficacy as monotherapy, or in combination with CTX, to improve OS of tumor-bearing mice. Using a syngeneic orthotopic mouse model for MM, our results indicate that reducing the presence of macrophages in MM significantly slows early, as well as late-stage MM growth, and improves response to standard-of-care CTX. These experimental findings indicate a protumoral role for macrophages in MM, and support clinical investigation of targeted therapies, in combination with CTX, for treatment of patients with MM."
"Collin Blakely, Tina Bose, Melissa Wheeler, Raphael Bueno, David Sugarbaker, David Jablons, V. Courtney Broaddus, Lisa Coussens. Macrophages foster neoplastic progression of malignant mesothelioma and limit response to chemotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4723. doi:10.1158/1538-7445.AM2013-4723"