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Zahra Souri, Annemijn Philine Annette Wierenga, Marijke Spruyt-Gerritse, Michael Eikmans, Martine J Jager; Regulation of PD-L1 in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):741.
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Both environmental and tumor-specific factors play a role in the regulation of the expression of PD-L1 in malignancies. We noticed a variable PD-L1 expression in uveal melanoma and set out to analyze which factors might determine PD-L1 expression.
Seven uveal melanoma cell lines were exposed to interferon-gamma, a known potent inducer of PDL1, to determine whether PD-L1 was sensitive to outside influence or not. We used HLA class I expression as control. Expression was determined by FACS analysis with PD-L1 (M1H1) and HLA Class I (W6/32) specific antibodies. PD-L1 expression was determined in 19 UM tissue samples by qPCR, and expression levels were compared.
Analysis of the PD-L1 expression on seven cell lines (92.1, Mel270, OMM2.5, OMM2.3, OMM1, XM66 and MP38) showed a comparable effect of interferon gamma on the expression of HLA Class I and PD-L1. We subsequently analyzed a set of primary UM to determine whether we could find a correlation between infiltrate and PD-L1. Similar to the known good correlation between HLA-A and –B levels and the presence of infiltrating T cells, a higher PD-L1 expression was observed in tumors containing an infiltrate (correlation test PD-L1 vs CD4 cells p = 0.02, vs CD8 p = 0.04, vs CD3 p = 0.09). Furthermore, a strong association was found between PD-L1 expression and expression of VEGF, IL4 and IL10 (p values < 0.001, <0.001, 0.002, respectively), all known as inducers of this checkpoint inhibitor in other tissues. We did not find a correlation with chromosome status.
Expression of PD-L1 on UM cell lines is upregulated in a similar fashion as HLA Class I by interferon-gamma, and expression in primary UM tissues shows a correlation between PD-L1 expression in the tissue and the presence of T lymphocytes. As VEGF expression was correlated with PD-L1 expression, we speculate that tissue-specific factors such as hypoxia instead of genetics influence PD-L1 expression.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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