Single-cell analysis reveals new evolutionary complexity in uveal melanoma

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…

• RT
  Research to Prevent Blindness

  Awards: P30EY014801, R01 CA125970
• MR
  Melanoma Research Alliance
• UO
  University of Miami

  Award: P30EY014801
• UO
  University of Washington
• SC
  Sylvester Comprehensive Cancer Center, University of Miami Health Systems

  Award: P30CA240139
• NI
  National Institutes of Health

  Awards: P30CA240139, CA125970, P30EY014801, R01 CA125970, Core Grant P30EY014801
• LM
  Leonard M. Miller School of Medicine

  Award: P30CA240139
• NC
  National Cancer Institute

  Awards: R01 CA125970, P30CA240139, CA125970