Dissecting cellular heterogeneity across two ocular melanoma subtypes by single-cell RNA sequencing.

Area of Science:

• Oncology
• Genomics
• Immunology

Background:

• Ocular melanoma is a rare but aggressive malignancy with poor prognosis.
• Understanding subtype-specific heterogeneity is crucial for targeted therapies.

Purpose of the Study:

• Investigate tumor cell and microenvironmental heterogeneity in uveal melanoma and conjunctival melanoma (CoM) at the single-cell level.
• Compare transcriptional profiles and immune infiltration between uveal melanoma and CoM.

Main Methods:

• Single-cell RNA sequencing performed on 28 ocular melanoma samples (14 uveal melanoma, 14 CoM).
• Analysis of tumor cells and immune cells to assess cellular composition and microenvironment.
• Transcriptome profiling to identify subtype-specific biological signatures.

Main Results:

• CoM exhibited significantly higher immune cell infiltration than uveal melanoma.
• CoM tumor cells showed distinct transcriptional states, including epithelial-mesenchymal transition and stemness programs, with higher copy number variation.
• Uveal melanoma featured CD8+ T cells with high cytotoxicity and exhaustion, while CoM had progenitor-like and exhausted effector features, plus increased M2-associated macrophages.

Conclusions:

• Single-cell analysis reveals distinct cellular compositions and molecular programs in uveal melanoma and CoM.
• CoM displays features associated with more aggressive tumor behavior and a unique immune microenvironment.
• Findings provide a comprehensive comparison of ocular melanoma subtypes, informing future therapeutic strategies.