Accession Number:

ADA555450

Title:

Role of Macrophage-Induced Inflammation in Mesothelioma

Descriptive Note:

Annual rept. 1 Jul 2010-30 Jun 2011

Corporate Author:

CALIFORNIA UNIV SAN FRANCISCO

Personal Author(s):

Report Date:

2011-07-01

Pagination or Media Count:

175.0

Abstract:

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.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE