Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment

IF 27.7 1区 医学 Q1 IMMUNOLOGY
Ruoyan Li, Johanna Strobl, Elizabeth F. M. Poyner, Aya Balbaa, Fereshteh Torabi, Pavel V. Mazin, Nana-Jane Chipampe, Emily Stephenson, Ciro Ramírez-Suástegi, Vijaya Baskar Mahalingam Shanmugiah, Louis Gardner, Bayanne Olabi, Rowen Coulthard, Rachel A. Botting, Nina Zila, Elena Prigmore, Nusayhah H. Gopee, Marta A. Chroscik, Efpraxia Kritikaki, Justin Engelbert, Issac Goh, Hon Man Chan, Harriet F. Johnson, Jasmine Ellis, Victoria Rowe, Win Tun, Gary Reynolds, Dexin Yang, April Rose Foster, Laure Gambardella, Elena Winheim, Chloe Admane, Benjamin Rumney, Lloyd Steele, Laura Jardine, Julia Nenonen, Keir Pickard, Jennifer Lumley, Philip Hampton, Simeng Hu, Fengjie Liu, Xiangjun Liu, David Horsfall, Daniela Basurto-Lozada, Louise Grimble, Chris M. Bacon, Sophie C. Weatherhead, Hanna Brauner, Yang Wang, Fan Bai, Nick J. Reynolds, Judith E. Allen, Constanze Jonak, Patrick M. Brunner, Sarah A. Teichmann, Muzlifah Haniffa
{"title":"Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment","authors":"Ruoyan Li, Johanna Strobl, Elizabeth F. M. Poyner, Aya Balbaa, Fereshteh Torabi, Pavel V. Mazin, Nana-Jane Chipampe, Emily Stephenson, Ciro Ramírez-Suástegi, Vijaya Baskar Mahalingam Shanmugiah, Louis Gardner, Bayanne Olabi, Rowen Coulthard, Rachel A. Botting, Nina Zila, Elena Prigmore, Nusayhah H. Gopee, Marta A. Chroscik, Efpraxia Kritikaki, Justin Engelbert, Issac Goh, Hon Man Chan, Harriet F. Johnson, Jasmine Ellis, Victoria Rowe, Win Tun, Gary Reynolds, Dexin Yang, April Rose Foster, Laure Gambardella, Elena Winheim, Chloe Admane, Benjamin Rumney, Lloyd Steele, Laura Jardine, Julia Nenonen, Keir Pickard, Jennifer Lumley, Philip Hampton, Simeng Hu, Fengjie Liu, Xiangjun Liu, David Horsfall, Daniela Basurto-Lozada, Louise Grimble, Chris M. Bacon, Sophie C. Weatherhead, Hanna Brauner, Yang Wang, Fan Bai, Nick J. Reynolds, Judith E. Allen, Constanze Jonak, Patrick M. Brunner, Sarah A. Teichmann, Muzlifah Haniffa","doi":"10.1038/s41590-024-02018-1","DOIUrl":null,"url":null,"abstract":"Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that can maintain TH2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL. Haniffa and colleagues provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for cutaneous T cell lymphoma.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2320-2330"},"PeriodicalIF":27.7000,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-02018-1.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41590-024-02018-1","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that can maintain TH2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL. Haniffa and colleagues provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for cutaneous T cell lymphoma.

Abstract Image

Abstract Image

皮肤 T 细胞淋巴瘤图谱揭示了由富含 B 细胞的肿瘤微环境支持的恶性 TH2 细胞
皮肤 T 细胞淋巴瘤(CTCL)是一种可能致命的 T 细胞克隆性恶性肿瘤,主要侵犯皮肤。最常见的皮肤 T 细胞淋巴瘤是真菌病,很难诊断,导致治疗延误。我们对真菌病型 CTCL 患者的皮肤进行了单细胞和空间转录组学分析,并与来自健康和炎症皮肤的人类皮肤细胞图谱数据集进行了综合比较分析。我们揭示了恶性 CTCL 细胞对 T 辅助 2(TH2)细胞免疫基因程序的共同选择,以及支持其生存的肿瘤微环境模型。我们发现了能维持TH2细胞样肿瘤细胞的MHC-II+成纤维细胞和树突状细胞。CTCL 肿瘤细胞在空间上与 B 细胞相关,形成三级淋巴结构样聚集。最后,我们在三个独立的患者队列中验证了 B 细胞在 CTCL 中的富集及其与疾病进展的关系。我们的发现为 CTCL 的诊断提供了帮助,为疾病分期和治疗策略提供了潜在的生物标记物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Nature Immunology
Nature Immunology 医学-免疫学
CiteScore
40.00
自引率
2.30%
发文量
248
审稿时长
4-8 weeks
期刊介绍: Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信