Immune Checkpoint Regulator in Ovarian Cancer Progression
Abstract
We hypothesize that CAF-derived MFAP5 can generate an immuno-suppressive microenvironment that suppresses CD8+ CTL activation by up-regulating CD47 expression in ovarian tumor cells and CD8+ CTLs and that inhibits CD8+ CTL trafficking through the extracellular matrix in the ovarian tumor microenvironment. A majority of experiments proposed under Major Goal 1 and a subset of experiments proposed under Major Goal 3has been accomplished. Our results demonstrated that a marked inverse correlation between stromal MFAP5expression and intraepithelial CD8+ T-cell density in high-grade serous ovarian tumor tissue samples. In addition, tumors developed in mice treated MFAP5-specific siRNAs or an anti-MFAP5 antibody had significantly lower CD47expression levels than in those treated with the control siRNA or the control IgG antibody, respectively. Preliminary studies also demonstrated that markedly lower intratumoral CD8+ T cell densities in mice treated with MFAP5-specific siRNAs than the control siRNA. Taken together, MFAP5 silencing or blockade in ovarian tumor bearing mice activate tumor infiltrating CD8+ T cells and down-regulate CD47 expression in tumor tissue.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2019
- Accession Number
- AD1090529
Entities
People
- Samuel C. Mok
Organizations
- University of Texas at Austin