Immune Checkpoint Regulator in Ovarian Cancer Progression
Technical Report,01 May 2018,30 Apr 2019
University of Texas MD Anderson Cancer Center Houston United States
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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.
- Medicine and Medical Research