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Lookup NU author(s): Dr Beth Poyner, Emily Stephenson, Dr Louis Gardner, Dr Bayanne Olabi, Dr Hudaa Gopee, Marta Chroscik, Effie Kritikaki, Justin Engelbert, Issac Goh, Dr Win Tun, Dr Gary Reynolds, Chloe Admane, Dr Laura JardineORCiD, Dr Keir Pickard, Jenny Lumley, Dr Philip Hampton, Dave Horsfall, Daniela Basurto Lozada, Louise Grimble, Dr Christopher Bacon, Dr Sophie Weatherhead, Professor Nick ReynoldsORCiD, Professor Muzlifah Haniffa
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024. 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.
Author(s): Li R, Strobl J, Poyner EFM, Balbaa A, Torabi F, Mazin PV, Chipampe N-J, Stephenson E, Ramirez-Suastegi C, Shanmugiah VBM, Gardner L, Olabi B, Coulthard R, Botting RA, Zila N, Prigmore E, Gopee NH, Chroscik MA, Kritikaki E, Engelbert J, Goh I, Chan HM, Johnson HF, Ellis J, Rowe V, Tun W, Reynolds G, Yang D, Foster AR, Gambardella L, Winheim E, Admane C, Rumney B, Steele L, Jardine L, Nenonen J, Pickard K, Lumley J, Hampton P, Hu S, Liu F, Liu X, Horsfall D, Basurto-Lozada D, Grimble L, Bacon CM, Weatherhead SC, Brauner H, Wang Y, Bai F, Reynolds NJ, Allen JE, Jonak C, Brunner PM, Teichmann SA, Haniffa M
Publication type: Article
Publication status: Published
Journal: Nature Immunology
Year: 2024
Volume: 25
Pages: 2320–2330
Print publication date: 01/12/2024
Online publication date: 18/11/2024
Acceptance date: 11/10/2024
Date deposited: 04/12/2024
ISSN (print): 1529-2908
ISSN (electronic): 1529-2916
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41590-024-02018-1
DOI: 10.1038/s41590-024-02018-1
Data Access Statement: There are no restrictions on data availability for newly generated data presented in the present study. FASTQ files of all raw sequencing data from the present study have been deposited at EMBL-EBI ArrayEx press and are made publicly available at accessions E-MTAB-14559, E-MTAB-12303 and E-MTAB-13614. Previously published scRNA-seq datasets are available in the Genome Sequence Archive for humans (accession HRA000166), the NCBI BioProject database (accession HRA000166), ArrayExpress (accession E-MTAB-8142) and the GEO database (accession GSE173205). Previously published bulk RNA-seq datasets are available in the GEO database under accessions GSE168508 and GSE121212. Scanpy h5ad objects for CTCL, CCL plus skin cell atlas and Visium data are available for download and can be explored on an online web portal: https://collections.cellatlas.io/ctcl. The code generated during the present study is available at GitHub: https://github.com/ruoyan-li/Cutaneous-T-cell-lymphoma-study
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