Journal Article

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

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

2024

Overview

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 (T H 2) 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 T H 2 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/580 / 631/61/514 / 631/67/580 / Biomarkers / Biomedical and Life Sciences / Biomedicine / Cell survival / Comparative analysis / Dendritic cells / Fungal infections / Helper cells / Immunology / Infectious Diseases / Inflammation / Lymphocytes / Lymphocytes B / Lymphocytes T / Lymphoma / Major histocompatibility complex / Malignancy / Mycosis / Mycosis fungoides / Resource / Skin / Spatial analysis / T-cell lymphoma / Transcriptomics / Tumor cells / Tumor microenvironment / Tumors