Single-cell profiling of acral melanoma infiltrating lymphocytes reveals a suppressive tumor microenvironment.

Autor: Minowa T; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan.; Department of Dermatology, Sapporo Medical University School of Medicine, 060-8543 Sapporo, Hokkaido, Japan., Murata K; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan.; Joint Research Center for Immunoproteogenomics, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan., Mizue Y; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan., Murai A; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan., Nakatsugawa M; Department of Pathology, Tokyo Medical University Hachioji Medical Center, 193-0998 Hachioji, Tokyo, Japan., Sasaki K; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan., Tokita S; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan.; Joint Research Center for Immunoproteogenomics, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan., Kubo T; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan., Kanaseki T; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan.; Joint Research Center for Immunoproteogenomics, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan., Tsukahara T; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan., Handa T; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan.; Department of Dermatology, Sapporo Medical University School of Medicine, 060-8543 Sapporo, Hokkaido, Japan., Sato S; Department of Dermatology, Sapporo Medical University School of Medicine, 060-8543 Sapporo, Hokkaido, Japan., Horimoto K; Department of Dermatology, Sapporo Medical University School of Medicine, 060-8543 Sapporo, Hokkaido, Japan., Kato J; Department of Dermatology, Sapporo Medical University School of Medicine, 060-8543 Sapporo, Hokkaido, Japan., Hida T; Department of Dermatology, Sapporo Medical University School of Medicine, 060-8543 Sapporo, Hokkaido, Japan., Hirohashi Y; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan., Uhara H; Department of Dermatology, Sapporo Medical University School of Medicine, 060-8543 Sapporo, Hokkaido, Japan., Torigoe T; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Hokkaido, Japan.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2024 Dec 04; Vol. 16 (776), pp. eadk8832. Date of Electronic Publication: 2024 Dec 04.
DOI: 10.1126/scitranslmed.adk8832
Abstrakt: Acral lentiginous melanoma (ALM) is the most common melanoma subtype in non-Caucasians. Despite advances in cancer immunotherapy, current immune checkpoint inhibitors remain unsatisfactory for ALM. Hence, we conducted comprehensive immune profiling using single-cell phenotyping with reactivity screening of the T cell receptors of tumor-infiltrating T lymphocytes (TILs) in ALM. Compared with cutaneous melanoma, ALM showed a lower frequency of tumor-reactive CD8 clusters and an enrichment of regulatory T cells with direct tumor recognition ability, suggesting a suppressive immune microenvironment in ALM. Tumor-reactive CD8 TILs showed heterogeneous expression of coinhibitory molecules, including KLRC1 (NKG2A), in subpopulations with therapeutic implications. Overall, our study provides a foundation for enhancing the efficacy of immunotherapy in ALM.
Databáze: MEDLINE
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