A single-cell analysis reveals tumor heterogeneity and immune environment of acral melanoma

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 () and Jilong Yang ()
Additional contact information
Chao Zhang: Tianjin Medical University
Hongru Shen: Tianjin Medical University
Tielong Yang: Tianjin Medical University
Ting Li: Tianjin Medical University
Xinyue Liu: Tianjin Medical University
Jin Wang: Tianjin Medical University
Zhichao Liao: Tianjin Medical University
Junqiang Wei: Tianjin Medical University
Jia Lu: Tianjin Medical University
Haotian Liu: Tianjin Medical University
Lijie Xiang: Tianjin Medical University
Yichen Yang: Tianjin Medical University
Meng Yang: Tianjin Medical University
Duan Wang: Sichuan University
Yang Li: Tianjin Medical University
Ruwei Xing: Tianjin Medical University
Sheng Teng: Tianjin Medical University
Jun Zhao: Tianjin Medical University
Yun Yang: Tianjin Medical University
Gang Zhao: Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
Kexin Chen: Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University
Xiangchun Li: Tianjin Medical University
Jilong Yang: Tianjin Medical University

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34877-3

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