Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment
Nature Immunology. 2024;25(12):2320-2330. DOI 10.1038/s41590-024-02018-1. PMID 39558094. PMCID PMC11588665.
How to cite
AMA
Li R, Strobl J, Poyner EFM, Balbaa A, Torabi F, Mazin PV, et al. Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment. Nat Immunol. 2024;25(12):2320-2330. doi:10.1038/s41590-024-02018-1APA
Li, R., Strobl, J., Poyner, E. F. M., Balbaa, A., Torabi, F., Mazin, P. V., et al. (2024). Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment. Nature Immunology, 25(12), 2320-2330. https://doi.org/10.1038/s41590-024-02018-1BibTeX
@article{li2024cutaneous,
title = {Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment},
author = {Li, R. and Strobl, J. and Poyner, E. F. M. and Balbaa, A. and Torabi, F. and Mazin, P. V. and others},
journal = {Nature Immunology},
volume = {25},
number = {12},
pages = {2320--2330},
year = {2024},
doi = {10.1038/s41590-024-02018-1},
pmid = {39558094}
}Mycosis fungoides, the most common cutaneous T cell lymphoma, is hard to catch early, when its patches and plaques look like eczema or psoriasis. To find what sets it apart, the authors assembled the largest single-cell and spatial map of the disease, profiling lesional skin from 45 patients and comparing it against healthy and inflamed skin.
The malignant T cells turned out to be reshaping their surroundings: taking on an allergy-like TH2 program, drawing support from specialized fibroblasts and dendritic cells, and pulling B cells into aggregates that resemble lymphoid tissue. Seeing where those cells actually sat in the skin, and not only which genes they switched on, is what connected the molecular story to the tissue itself.
Key findings
- The largest single-cell and spatial atlas of cutaneous T cell lymphoma skin. Single-cell RNA and T cell receptor sequencing across 45 patients — spanning early and advanced disease — captured roughly 420,000 cells and was integrated with a healthy and inflamed skin reference to isolate features specific to the lymphoma.
- Malignant T cells co-opt an allergy-like TH2 program that their microenvironment sustains. Advanced-stage tumor cells shifted toward a GATA3-driven TH2-like state (P = 0.0003), supported by MHC-II+ fibroblasts and dendritic cells predicted to signal directly to the malignant cells.
- B cells fill the tumor microenvironment in direct contact with malignant T cells, and track with worse outcomes. Multiplex protein imaging and spatial transcriptomics placed CD20+ B cells against CD4+ malignant T cells in the tissue; B cell enrichment was confirmed across three independent cohorts and rose with disease progression and poorer survival.
Orion in the methods
“Finally, slides were coverslipped using ArgoFluor mounting medium (RareCyte, 241301000) and imaged on the following day using a RareCyte Orion microscope with a ×20 objective. Scans were performed using Imager and relevant acquisition settings were applied using the software Artemis.”
— Li et al., Nature Immunology (2024), Methods, “RareCyte 16-plex immunofluorescence staining”
Why it matters for Orion users
If you are considering Orion for a tissue study, look at the job its imaging arm was given here. The atlas was assembled from dissociated single cells and from spatial transcriptomics, which predict where cell types sit but read protein identity only indirectly. Orion was asked to confirm, at the protein level and in the intact section, the neighborhood those methods proposed: that CD20+ B cells sit in direct contact with CD4+ malignant T cells. Answering that needs single-cell measurements read in place across a whole skin section, with enough markers to separate B cells, malignant and benign T cells, myeloid cells and the tissue’s own structure at once. Here all sixteen markers were captured in a single staining round, and the resulting images placed B cells against tumor cells across eight patients stained in triplicate. That is what turned a predicted co-localization into a directly observed one, the spatial evidence behind the study’s case that B cells define the cutaneous T cell lymphoma microenvironment.
