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Implantation and Evaluation of Melanoma in the Murine Choroid via Optical Coherence Tomography
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Single-cell analysis reveals new evolutionary complexity in uveal melanoma
Michael A Durante1,2,3, Daniel A Rodriguez1,2,3, Stefan Kurtenbach1,2,3
1Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
Nature Communications
|January 26, 2020
Summary
Uveal melanoma (UM) is a metastatic cancer resistant to immunotherapy. This study reveals a diverse tumor microenvironment, identifying LAG3 as a potential target for new UM treatments.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Uveal melanoma (UM) is a rare, highly metastatic eye cancer.
- UM is largely unresponsive to current immune checkpoint therapies, unlike cutaneous melanoma.
Purpose of the Study:
- To investigate the tumor microenvironment of uveal melanoma at single-cell resolution.
- To identify novel therapeutic targets for UM treatment.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of 59,915 cells from primary and metastatic UM samples.
- V(D)J sequencing to analyze T cell receptor repertoire and clonal expansion.
Main Results:
- Discovered novel subclonal genomic complexity and transcriptional states in UM cells.
- Identified a diverse immune cell infiltrate, with CD8+ T cells expressing LAG3 predominantly over PD1 or CTLA4.
- Observed clonally expanded T cells and plasma cells in metastatic samples, indicating immune responses.
Conclusions:
- The UM tumor microenvironment harbors a complex ecosystem of tumor and immune cells.
- LAG3 is a promising target for immune checkpoint blockade therapy in high-risk UM patients.
