Single-cell analysis reveals new evolutionary complexity in uveal melanoma.
Michael A DuranteDaniel A RodriguezStefan KurtenbachJeffim N KuznetsovMargaret I SanchezChristina L DecaturHelen SnyderLynn G FeunAlan S LivingstoneJ William HarbourPublished in: Nature communications (2020)
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.
Keyphrases
- single cell
- rna seq
- immune response
- dna damage
- high throughput
- squamous cell carcinoma
- small cell lung cancer
- skin cancer
- cell cycle
- genome wide
- induced apoptosis
- papillary thyroid
- climate change
- magnetic resonance
- gene expression
- human health
- cell cycle arrest
- basal cell carcinoma
- transcription factor
- risk assessment
- squamous cell
- young adults
- dna methylation
- toll like receptor
- cell death
- cell proliferation
- contrast enhanced
- heat shock
- pi k akt