Faculty, Staff and Student Publications
Publication Date
12-1-2024
Journal
Nature Immunology
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.
Keywords
Humans, Tumor Microenvironment, Lymphoma, T-Cell, Cutaneous, Th2 Cells, Skin Neoplasms, B-Lymphocytes, Skin, Single-Cell Analysis, Fibroblasts, Gene Expression Regulation, Neoplastic, Dendritic Cells, Transcriptome, Tumour immunology, Tumour immunology, Sequencing
DOI
10.1038/s41590-024-02018-1
PMID
39558094
PMCID
PMC11588665
PubMedCentral® Posted Date
11-18-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons
Comments
This article has been corrected. See Nat Immunol. 2024 Dec 2;26(1):147.