Single-cell analysis reveals new evolutionary complexity in uveal melanoma

Michael A. Durante, Daniel A. Rodriguez, Stefan Kurtenbach, Jeffim N. Kuznetsov, Margaret I. Sanchez, Christina L. Decatur, Helen Snyder, Lynn G. Feun, Alan S. Livingstone and J. William Harbour ()
Additional contact information
Michael A. Durante: University of Miami Miller School of Medicine
Daniel A. Rodriguez: University of Miami Miller School of Medicine
Stefan Kurtenbach: University of Miami Miller School of Medicine
Jeffim N. Kuznetsov: University of Miami Miller School of Medicine
Margaret I. Sanchez: University of Miami Miller School of Medicine
Christina L. Decatur: University of Miami Miller School of Medicine
Helen Snyder: Cell IDx Inc.
Lynn G. Feun: University of Miami Miller School of Medicine
Alan S. Livingstone: University of Miami Miller School of Medicine
J. William Harbour: University of Miami Miller School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract Uveal melanoma (UM) is a highly metastatic cancer that, in contrast to cutaneous melanoma, is largely unresponsive to checkpoint immunotherapy. Here, we interrogate the tumor microenvironment at single-cell resolution using scRNA-seq of 59,915 tumor and non-neoplastic cells from 8 primary and 3 metastatic samples. Tumor cells reveal novel subclonal genomic complexity and transcriptional states. Tumor-infiltrating immune cells comprise a previously unrecognized diversity of cell types, including CD8+ T cells predominantly expressing the checkpoint marker LAG3, rather than PD1 or CTLA4. V(D)J analysis shows clonally expanded T cells, indicating that they are capable of mounting an immune response. An indolent liver metastasis from a class 1B UM is infiltrated with clonally expanded plasma cells, indicative of antibody-mediated immunity. This complex ecosystem of tumor and immune cells provides new insights into UM biology, and LAG3 is identified as a potential candidate for immune checkpoint blockade in patients with high risk UM.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-14256-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14256-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-14256-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().