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Single cell characterization of the cellular landscape of acral melanoma identifies novel targets for immunotherapy

ABSTRACT: Single cell characterization of the cellular landscape of acral melanoma identifies novel targets for immunotherapy

PROVIDER: PRJNA784961 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17075100.fastq.gz	Fastqsanger.gz
	SRR17075101.fastq.gz	Fastqsanger.gz
	SRR17075102.fastq.gz	Fastqsanger.gz
	SRR17075103.fastq.gz	Fastqsanger.gz
	SRR17075104.fastq.gz	Fastqsanger.gz

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Single cell characterization of the cellular landscape of acral melanoma identifies novel targets for immunotherapy

Project description:Acral melanoma is a rare subtype of melanoma that arises on the non-hair-bearing skin of the palms, soles and nail beds. In this study, we used single cell RNA-seq (scRNA-seq) to map the transcriptional landscape of acral melanoma and identify novel immunotherapeutic targets.

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Project description:Assessment of mutation on expression levels Transcriptomic profile of a matched primary and metastatic acral melanoma One Primary and one metastatic acral melanoma transcript expression were assayed (no matched normal)

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Genome wide analysis of acral melanoma (Affymetrix)

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Single-cell Characterization of the Cellular Landscape of Acral Melanoma Identifies Novel Targets for Immunotherapy.

Project description:PurposeAcral melanoma is a rare subtype of melanoma that arises on the non-hair-bearing skin of the palms, soles, and nail beds. In this study, we used single-cell RNA sequencing (scRNA-seq) to map the transcriptional landscape of acral melanoma and identify novel immunotherapeutic targets.Experimental designWe performed scRNA-seq on nine clinical specimens (five primary, four metastases) of acral melanoma. Detailed cell type curation was performed, the immune landscapes were mapped, and key results were validated by analysis of The Cancer Genome Atlas (TCGA) and single-cell datasets. Cell-cell interactions were inferred and compared with those in nonacral cutaneous melanoma.ResultsMultiple phenotypic subsets of T cells, natural killer (NK) cells, B cells, macrophages, and dendritic cells with varying levels of activation/exhaustion were identified. A comparison between primary and metastatic acral melanoma identified gene signatures associated with changes in immune responses and metabolism. Acral melanoma was characterized by a lower overall immune infiltrate, fewer effector CD8 T cells and NK cells, and a near-complete absence of γδ T cells compared with nonacral cutaneous melanomas. Immune cells associated with acral melanoma exhibited expression of multiple checkpoints including PD-1, LAG-3, CTLA-4, V-domain immunoglobin suppressor of T cell activation (VISTA), TIGIT, and the Adenosine A2A receptor (ADORA2). VISTA was expressed in 58.3% of myeloid cells and TIGIT was expressed in 22.3% of T/NK cells.ConclusionsAcral melanoma has a suppressed immune environment compared with that of cutaneous melanoma from nonacral skin. Expression of multiple, therapeutically tractable immune checkpoints were observed, offering new options for clinical translation.

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Molecular characterization of acral melanoma

Project description:Molecular characterization of acral melanoma

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