免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
通过整合单细胞和空间转录组分析，描绘肢端黑色素瘤的早期播散机制
英文原题：Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses.
查看英文原题
Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses.
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中文摘要
肢端黑色素瘤（AM）是一种罕见的黑色素瘤亚型，其特征是淋巴结（LN）转移发生率高，而淋巴结转移是肿瘤播散和治疗决策的关键因素。在此，我们采用单细胞和空间转录组分析来研究早期AM播散的动态演化。我们的研究结果揭示了AM中存在显著的肿瘤间和肿瘤内异质性，同时伴有高度免疫抑制的肿瘤微环境和复杂的细胞间通讯网络，尤其是在淋巴结转移患者中。值得注意的是，我们发现MYC + 黑色素瘤（MYC + MEL）和FGFBP2 + NKT细胞与淋巴结转移之间存在强关联。此外，我们证明淋巴结转移需要MYC + MEL细胞中由MITF诱导的向脂肪酸氧化（FAO）的代谢转变。依托莫司（Etomoxir），一种临床批准的FAO抑制剂，可以有效抑制MITF介导的淋巴结转移。这一综合数据集增强了我们对AM中淋巴结转移的理解，并为早期AM播散管理的潜在治疗靶向提供了见解。
展开英文摘要原文
Acral melanoma (AM) is a rare subtype of melanoma characterized by a high incidence of lymph node (LN) metastasis, a critical factor in tumor dissemination and therapeutic decision-making.
Here, we employ single-cell and spatial transcriptomic analyses to investigate the dynamic evolution of early AM dissemination.
Our findings reveal substantial inter- and intra-tumor heterogeneity in AM, alongside a highly immunosuppressive tumor microenvironment and complex intercellular communication networks, particularly in patients with LN metastasis.
Notably, we identify a strong association between MYC + Melanoma (MYC + MEL) and FGFBP2 + NKT cells with LN metastasis.
Furthermore, we demonstrate that LN metastasis requires a metabolic shift towards fatty acid oxidation (FAO) induced by MITF in MYC + MEL cells. Etomoxir, a clinically approved FAO inhibitor, can effectively suppress MITF-mediated LN metastasis. This comprehensive dataset enhances our understanding of LN metastasis in AM, and provides insights into the potential therapeutic targeting for the management of early AM dissemination.
论文信息
- 作者
- Wei C、Sun W、Shen K、Zhong J、Liu W、Gao Z、Xu Y、Wang L
- 第一作者单位
- Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.China
- 通讯作者单位
- Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China. prof_jianyinggu@163.com.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Nature communications2023 Dec 8
- 原文标识
- PubMed 38065972 · DOI 10.1038/s41467-023-43980-y
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