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.

中文翻译：

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肢端黑色素瘤浸润淋巴细胞的单细胞分析揭示了抑制性肿瘤微环境


肢端雀斑样黑色素瘤 （ALM） 是非白种人中最常见的黑色素瘤亚型。尽管癌症免疫疗法取得了进展，但目前的免疫检查点抑制剂对 ALM 仍然不令人满意。因此，我们使用单细胞表型对 ALM 中肿瘤浸润性 T 淋巴细胞 （TIL） 的 T 细胞受体进行反应性筛选进行了全面的免疫分析。与皮肤黑色素瘤相比，ALM 显示肿瘤反应性 CD8 簇的频率较低，并且具有直接肿瘤识别能力的调节性 T 细胞丰富，表明 ALM 中存在抑制性免疫微环境。肿瘤反应性 CD8 TILs 在具有治疗意义的亚群中显示共抑制分子的异质性表达，包括 KLRC1 （NKG2A）。总的来说，我们的研究为提高免疫疗法在 ALM 中的疗效提供了基础。