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, Lu Jia, 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
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.