Abstract 1591: Single cell analysis of uveal melanoma reveals new evolutionary complexity

Uveal melanoma (UM) is a highly metastatic cancer that is largely unresponsive to molecular and immune therapy. We used scRNA-seq and other methods to analyze 59,915 tumor and non-neoplastic cells from 8 primary and 3 metastatic UMs. This analysis confirmed the class 1/class 2 transcriptomic landscape established from bulk analysis and revealed newly identified subclonal genomic complexity and transcriptional states consistent with phenotype plasticity. The immune compartment comprised a previously unappreciated diversity of cell types. There was low expression of CTLA4 and PD1, but strong expression of a different checkpoint molecule. These findings revealed a dynamic ecosystem in which UM and immune cells co-evolve along trajectories associated with specific genomic aberrations, and they may explain the poor response of UM to current immunotherapy regimens. We identified a new promising candidate for immune checkpoint blockade in metastatic UM. Citation Format: Michael A. Durante, Daniel A. Rodriguez, Stefan Kurtenbach, Jeffim N. Kuznetsoff, Margaret I. Sanchez, Christina L. Decatur, Helen Snyder, Lynn G. Feun, Alan S. Livingstone, J. William Harbour. Single cell analysis of uveal melanoma reveals new evolutionary complexity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1591.