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

Acral melanoma is a dismal subtype of melanoma occurring in glabrous acral skin, and accounts for about 50% of darker-skinned melanoma patients. We performed single-cell RNA sequencing for 63,394 cells obtained from 5 acral and 3 cutaneous melanoma samples to investigate tumor cellular ecosystem particularly the heterogeneity and immune environment. We defined 5 orthogonal functional cell clusters that were involved in TGF-beta signaling, Type I interferon, Wnt signaling, Cell cycle, and Cholesterol efflux signaling. Signatures of TGF-beta signaling and cholesterol efflux are significantly associated with prognosis of melanoma. Compared with cutaneous melanoma, acral melanoma samples had significantly severe immunosuppressive state including depletion of cytotoxic CD8+ T cells, enrichment of Treg cells, and exhausted CD8+ T cells. PD1 and TIM-3 had higher expression in the exhaustive CD8+ T cells of acral melanoma. In summary, we have uncovered the tumor heterogeneity and immune infiltration characteristics of acral melanoma. Our findings may help to understand and guide the immunotherapy of acral melanoma.