Dataset Information

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

ABSTRACT:

Purpose

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 sequencing (scRNA-seq) to map the transcriptional landscape of acral melanoma and identify novel immunotherapeutic targets.

Experimental design

We 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.

Results

Multiple 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.

Conclusions

Acral 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.

SUBMITTER: Li J

PROVIDER: S-EPMC9106889 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

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

Li Jiannong J Smalley Inna I Chen Zhihua Z Wu Jheng-Yu JY Phadke Manali S MS Teer Jamie K JK Nguyen Thanh T Karreth Florian A FA Koomen John M JM Sarnaik Amod A AA Zager Jonathan S JS Khushalani Nikhil I NI Tarhini Ahmad A AA Sondak Vernon K VK Rodriguez Paulo C PC Messina Jane L JL Chen Y Ann YA Smalley Keiran S M KSM

Clinical cancer research : an official journal of the American Association for Cancer Research 20220501 10

<h4>Purpose</h4>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 sequencing (scRNA-seq) to map the transcriptional landscape of acral melanoma and identify novel immunotherapeutic targets.<h4>Experimental design</h4>We performed scRNA-seq on nine clinical specimens (five primary, four metastases) of acral melanoma. Detailed cell type curation was performed, the immune landscapes were m ...[more]

PMID: 35247927

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Project description:BackgroundPulmonary arterial hypertension (PAH) is a critical cardiopulmonary vascular disorder marked by the progressive elevation of pulmonary artery pressure, increased pulmonary vascular resistance, and eventual right heart failure. Research has shown that various immune cells play a significant role in the pathogenesis of PAH, both in patients diagnosed with the condition and in experimental models of PAH. Cell-cell communication is important for PAH progression and therapies, while the global cell landscape of intercellular signaling has not been elucidated.MethodsWe performed single-cell RNA sequencing on NCBI Gene Expression Omnibus (GEO) databases GSE169471, GSE 210248, GSE228643 and GSE244781, and analyzed lung tissue samples across healthy controls and PAH patients. In total, approximately 124,561 cells were analyzed and a total 34 clusters were identified. We integrated the sequencing results of multiple samples and used an enhanced single-cell sequencing workflow to overcome the limitations of a single study.ResultsIn this study, we elucidated the functional characteristics and potential regulatory interactions of several cell subpopulations that have not been previously documented in similar research. We constructed a comprehensive landscape of cell communications at the single-cell resolution, which is expected to significantly advance the development of personalized diagnostic and therapeutic strategies for PAH. We demonstrated the transcriptomic features of different cell types in PAH patients. We presented an in-depth analysis of T cell subsets, myeloid cell heterogeneity and a comprehensive analysis of SMCs and FBs subsets in PAH. T cell heterogeneity and functional dynamics were exhibited in PAH, which suggests that targeting cytotoxic regulation may be a potential therapeutic strategy. Significant changes and potential functions of myeloid cell subsets in PAH patients and we especially focused on GPNMB+ macrophages. In addition, CellChat and NicheNet analyses reveal altered intercellular communication and dys-regulated signaling pathways in PAH progression. The enhanced MIF and IL-1 signaling suggests that the induced inflammatory response in PAH is greatly driven.ConclusionsWe systematically explored the immune heterogeneity and population and target cells in PAH, which may be valuable for developing new and precise therapies.

Dataset Information

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

Purpose

Experimental design

Results

Conclusions

Publications

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

Similar Datasets

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