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

IF 15.8 1区医学 Q1 CELL BIOLOGY Science Translational Medicine Pub Date : 2024-12-04 DOI:10.1126/scitranslmed.adk8832

Tomoyuki Minowa, Kenji Murata, Yuka Mizue, Aiko Murai, Munehide Nakatsugawa, Kenta Sasaki, Serina Tokita, Terufumi Kubo, Takayuki Kanaseki, Tomohide Tsukahara, Toshiya Handa, Sayuri Sato, Kohei Horimoto, Junji Kato, Tokimasa Hida, Yoshihiko Hirohashi, Hisashi Uhara, Toshihiko Torigoe

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Abstract

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.

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肢端黑色素瘤浸润淋巴细胞的单细胞谱显示了一个抑制性肿瘤微环境

肢端色素性黑色素瘤（ALM）是非白种人中最常见的黑色素瘤亚型。尽管癌症免疫治疗取得了进展，但目前的免疫检查点抑制剂对ALM仍然不满意。因此，我们使用单细胞表型和反应性筛选肿瘤浸润T淋巴细胞（TILs）的T细胞受体进行了全面的免疫分析。与皮肤黑色素瘤相比，ALM显示出较低的肿瘤反应性CD8簇频率和具有直接肿瘤识别能力的调节性T细胞的富集，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表达，包括KLRC1 （NKG2A）。总之，我们的研究为提高免疫治疗在ALM中的疗效提供了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

26.70

自引率

1.20%

发文量

309

审稿时长

1.7 months

期刊介绍： Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.