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. 2023 Mar;143(3):521-524.e3.
doi: 10.1016/j.jid.2022.08.047. Epub 2022 Sep 16.

CD8+ T Lymphocytes in Hypopigmented Mycosis Fungoides: Malignant Cells or Reactive Clone?

Simon Cao  1 , Oleg Kruglov  2 , Oleg E Akilov  3
Affiliations

CD8+ T Lymphocytes in Hypopigmented Mycosis Fungoides: Malignant Cells or Reactive Clone?

Simon Cao et al. J Invest Dermatol. 2023 Mar.
No abstract available

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Conflict of interest statement

CONFLICT OF INTEREST

OEA has received research funding/grant support from Actelion, Adaptive Biotechnology, Trillium Therapeutics, Pfizer, Kyowa Kirin, and Malinkrodt; serves as a principal investigator on current clinical trials: Trillium, Eisai, Affimed, Innate Pharma, Tellomak, and Corvus; OEA is a consultant for Castle Biomarkers, SkinJet, Bioniz, Kyowa-Hakka-Kirin, and Allmiral; and OEA is a speaker for Kyowa Kirin and Helsin. The remaining authors state no conflict of interest.

Figures

Figure 1.
Figure 1.. Reference mapping model accurately predicts malignant CD4+ T cells in classic MF.
(a) UMAP of targeted scRNA-seq in one patient with classic MF (GEO accession number GSM5280111) and identification of malignant and nonmalignant cell types of the tumor microenvironment. (b) UMAP of scRNA-seq in a second patient with classic MF (GEO accession number GSM5047045). (c) Heatmap of cell clusters in GSM5280111. Genes with the greatest differential expression in each region are listed. (d) Identification of the top 20 differentially expressed genes of the malignant CD4+ T-cell population in GSM5280111. (e) Reference mapping prediction of malignant cells in GSM5047045 using a model built on GSM5280111. (f) Reference mapping prediction of malignant cells in normal skin, psoriasis, atopic dermatitis, and vitiligo samples using the model. (g) Reference mapping prediction of malignant cells in GSM5047045, excluding CD4 from the model. AUC, area under the curve; DC, dendritic cell; GEO, Gene Expression Omnibus; MF, mycosis fungoides; scRNA-seq, single-cell RNA sequencing; T-reg, regulatory T cell; UMAP, Uniform Manifold Approximation and Projection.
Figure 2.
Figure 2.. Targeted scRNA-seq and reference mapping analysis of one patient with HMF indicates a malignant CD4+ T-cell population separate from clonal CD8+ T cells.
(a) Hypopigmented patch. (b) Atypical CD8+ epidermotropic lymphocytes on skin biopsy (H&E, CD4, and CD8 staining; bar = 50 μm). (c) UMAP projection of scRNA-seq from a patient with HMF. (d) Reference mapping prediction of malignant cells in a patient with HMF using model built on GSM5280111. Clustering of clonal T cells, CD4+ T cells, and CD8+ T cells are also shown. (e) TCR-α CDR3 amino acid sequences in CD8+ T cells. (f) TCR-α CDR3 amino acid sequences in predicted malignant T cells. (g) Dot plot of the top 20 differentially expressed genes used in the reference mapping model showing gene expression in clonal CD8+ T cells, polyclonal CD8+ T cells, nonmalignant CD4+ T cells, and predicted malignant cells in the patient with HMF. HMF, hypopigmented mycosis fungoides; scRNA-seq, single-cell RNA sequencing; STAT4, singal transducer and activator of transcription 4; UMAP, Uniform Manifold Approximation and Projection.
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