A Single-cell Analysis Reveals Tumor Heterogeneity and Immune Environment of Acral Melanoma

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Nov 26

PMID 36433984

Authors

Chao Zhang

Hongru Shen

Tielong Yang

Ting Li

Xinyue Liu

Jin Wang

Zhichao Liao

Junqiang Wei

Jia Lu

Haotian Liu

Lijie Xiang

Yichen Yang

Meng Yang

Duan Wang

Yang Li

Ruwei Xing

Sheng Teng

Jun Zhao

Yun Yang

Gang Zhao

Kexin Chen

Xiangchun Li

Jilong Yang

Affiliations

Soon will be listed here.

Abstract

Acral melanoma is a dismal subtype of melanoma occurring in glabrous acral skin, and has a higher incidence in East Asians. We perform single-cell RNA sequencing for 63,394 cells obtained from 5 acral and 3 cutaneous melanoma samples to investigate tumor heterogeneity and immune environment. We define 5 orthogonal functional cell clusters that are involved in TGF-beta signaling, Type I interferon, Wnt signaling, Cell cycle, and Cholesterol efflux signaling. Signatures of enriched TGF-beta, Type I interferon, and cholesterol efflux signaling are significantly associated with good prognosis of melanoma. Compared with cutaneous melanoma, acral melanoma samples have significantly severe immunosuppressive state including depletion of cytotoxic CD8+ T cells, enrichment of Treg cells, and exhausted CD8+ T cells. PD1 and TIM-3 have higher expression in the exhaustive CD8+ T cells of acral melanoma. Key findings are verified in two independent validation sets. This study contributes to our better understanding of acral melanoma.

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