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DOI 10.1038/s41590-024-02018-1

Медицинская библиотека · Nature immunology · 2024

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

Li Ruoyan, Strobl Johanna, Poyner Elizabeth F M, Balbaa Aya, Torabi Fereshteh, Mazin Pavel V, Chipampe Nana-Jane, Stephenson Emily, Ramírez-Suástegi Ciro, Shanmugiah Vijaya Baskar Mahalingam, Gardner Louis, Olabi Bayanne, Coulthard Rowen, Botting Rachel A, Zila Nina, Prigmore Elena, Gopee Nusayhah H, Chroscik Marta A, Kritikaki Efpraxia, Engelbert Justin, Goh Issac, Chan Hon Man, Johnson Harriet F, Ellis Jasmine, Rowe Victoria, Tun Win, Reynolds Gary, Yang Dexin, Foster April Rose, Gambardella Laure, Winheim Elena, Admane Chloe, Rumney Benjamin, Steele Lloyd, Jardine Laura, Nenonen Julia, Pickard Keir, Lumley Jennifer, Hampton Philip, Hu Simeng, Liu Fengjie, Liu Xiangjun, Horsfall David, Basurto-Lozada Daniela, Grimble Louise, Bacon Chris M, Weatherhead Sophie C, Brauner Hanna, Wang Yang, Bai Fan, Reynolds Nick J, Allen Judith E, Jonak Constanze, Brunner Patrick M, Teichmann Sarah A, Haniffa Muzlifah

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Аннотация

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.

Для цитирования: Li Ruoyan, Strobl Johanna, Poyner Elizabeth F M, Balbaa Aya, Torabi Fereshteh, Mazin Pavel V, Chipampe Nana-Jane, Stephenson Emily, Ramírez-Suástegi Ciro, Shanmugiah Vijaya Baskar Mahalingam, Gardner Louis, Olabi Bayanne, Coulthard Rowen, Botting Rachel A, Zila Nina, Prigmore Elena, Gopee Nusayhah H, Chroscik Marta A, Kritikaki Efpraxia, Engelbert Justin, Goh Issac, Chan Hon Man, Johnson Harriet F, Ellis Jasmine, Rowe Victoria, Tun Win, Reynolds Gary, Yang Dexin, Foster April Rose, Gambardella Laure, Winheim Elena, Admane Chloe, Rumney Benjamin, Steele Lloyd, Jardine Laura, Nenonen Julia, Pickard Keir, Lumley Jennifer, Hampton Philip, Hu Simeng, Liu Fengjie, Liu Xiangjun, Horsfall David, Basurto-Lozada Daniela, Grimble Louise, Bacon Chris M, Weatherhead Sophie C, Brauner Hanna, Wang Yang, Bai Fan, Reynolds Nick J, Allen Judith E, Jonak Constanze, Brunner Patrick M, Teichmann Sarah A, Haniffa Muzlifah. Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment.. Nature immunology. 2024. DOI: 10.1038/s41590-024-02018-1.

Предметные рубрики MeSH

HumansTumor MicroenvironmentLymphoma, T-Cell, CutaneousTh2 CellsSkin NeoplasmsB-LymphocytesSkinSingle-Cell AnalysisFibroblastsGene Expression Regulation, NeoplasticDendritic CellsTranscriptome
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