Immune Checkpoint Regulator in Ovarian Cancer Progression
Technical Report,01 May 2017,30 Apr 2018
University of Texas,M.D. 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 3 has been accomplished. Our results demonstrated that a marked inverse correlation between stromal MFAP5 expression 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 CD47 expression 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