Understanding and Targeting Tumor Microenvironment in Prostate Cancer to Inhibit Tumor Progression and Castration Resistance
Abstract
The signaling mechanisms between prostate cancer cells and infiltrating immune cells may illuminate novel therapeutic approaches. During the first year of the award period, utilizing a prostate adenocarcinoma model driven by loss of Pten and Smad4, I identified polymorphonuclear myeloid-derived suppressor cells (MDSCs) as the major infiltrating immune cell type which accumulates in the tumor microenvironment and in circulation as the cancer progresses. The MDSCs display potent immunosuppressive activity to limit T cell proliferation. Importantly, depletion of MDSCs with either anti-Gr1 antibody or a MDSC-targeting peptibody blocked tumor progression in mice. Employing a novel dual reporter prostate cancer model, epithelial and stromal transcriptomic profiling identified Cxcl5 as a possible cancer-secreted chemokine to attract Cxcr2-expressing MDSCs. Overall, the research accomplished the proposed and approved Statement of Work for the first year and laid a solid foundation for next two years.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1001738
Entities
People
- Xin Lu
Organizations
- University of Texas at Austin