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

2024/11/18 by Ruoyan Li, Johanna Strobl, Elizabeth Poyner +53 · 1 voice
Medicine · Immunology and Microbiology · #Cutaneous lymphoproliferative disorders research #T-cell and B-cell Immunology #CAR-T cell therapy research

paper · doi:10.1038/s41590-024-02018-1

openalex publication_date 2024/11/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/03

Abstract

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 (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.

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