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Kinya Tsubota, Yoshihiko Usui, Hiroshi Goto; Cell population having a resistance to melanoma antigen specific T cell in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):735.
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Therapeutic effect of immune check point blockade including blocking programmed cell death protein 1 (PD-1), programmed death-ligand (PD-L1), or cytotoxic T lymphocyte antigen-4 (CTLA-4) have improved outcome in patients with advanced malignant tumors refractory to the conventional treatments. On the other hands, it is important issue that the existence of many immune check point blockade-resistant malignant tumors. Recently heterogeneity in some malignant tumors has attracted much attention as a mechanism of resistance to treatment. Exist of small cell population having a resistance to treatment is one reason of treatment failure or metastasis. In this study, we analyzed the heterogeneity in uveal melanoma cell lines using flow cytometry and explored the cell population having a resistance to melanoma antigen specific T cell.
Three uveal melanoma cell lines; 92-1, OMM1 and TMU (established in Tokyo Medical University), were analyzed using flow cytometry after immunostaining (CD9, CD10, CD29, CD44, CD49b, CD49d, CD49e, CD49f, CD54, CD57, CD63, CD117, CD133, CD151, CD166, CD171, CD271, CD324 and A2B5). To identify cell surface markers for heterogeneity, we explored cell surface markers that can divide uveal melanoma cell line into 2 groups (positive and negative) by fluorescence intensity. Moreover, we co-cultured each uveal melanoma cell line (divided into positive and negative groups) and MART-1 specific T cells with melanoma antigen-specific cytotoxic T cells, and compared IFN-γ production between positive and negative cells.
Three cell surface markers; CD57, CD151 and CD271, were able to divide all cell lines into positive and negative groups based on fluorescence intensity. The production of IFN-γ decreased in CD57-, CD151+ and CD271+ cells compared to CD57+, CD151- and CD271- cells, respectively.
These results suggest the existence of heterogeneity and populations of cells that are resistant to treatment in uveal melanoma cell line. Heterogeneity among melanoma cells may account for the finding of some uveal melanomas refractory to conventional treatment.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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