Single-cell RNA sequencing comparison of CD4+, CD8+ and TCR-γδ+ cutaneous T-cell lymphomas reveals subset-specific molecular phenotypes.

IF 11 1区医学 Q1 DERMATOLOGY

British Journal of Dermatology Pub Date : 2024-08-12 DOI:10.1093/bjd/ljae313

Sumanth Chennareddy, Katharina Rindler, John R Ruggiero, Natalia Alkon, Emry R Cohenour, Sophia Tran, Wolfgang Weninger, Johannes Griss, Constanze Jonak, Patrick M Brunner

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引用次数: 0

Abstract

Background: Malignant clones of primary cutaneous T-cell lymphomas (CTCL) can show a CD4, CD8 or TCR-γδ phenotype, but their individual impact on tumor biology and skin lesion formation remains ill-defined.

Objectives: To perform a comprehensive molecular characterization of CD4+ vs. CD8+ and TCR-γ/δ+ CTCL lesions.

Methods: We performed scRNA-seq of 18 CTCL skin biopsies to compare classic CD4+ advanced-stage mycosis fungoides (MF) with TCR-γ/δ+MF and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (Berti's lymphoma).

Results: Malignant clones of TCR-γ/δ+MF and Berti's lymphoma showed similar clustering patterns distinct from CD4+MF, along with increased expression of cytotoxic markers such as NKG7, CTSW, GZMA, and GZMM. Only advanced-stage CD4+MF clones expressed central memory T-cell markers (SELL, CCR7, LEF1), alongside B1/B2 blood involvement, whereas TCR-γ/δ+MF and Berti's lymphoma harbored a more tissue-resident phenotype (CD69, CXCR4, NR4A1) without detectable cells in the blood. CD4+MF and TCR-γ/δ+MF skin lesions harbored strong type 2 immune activation across myeloid cells, while Berti's lymphoma was more skewed towards type 1 immune responses. Both CD4+MF and TCR-γ/δ+MF lesions showed upregulation of keratinocyte hyperactivation markers such as S100As and KRT16 genes. This increase was entirely absent in Berti's lymphoma, possibly reflecting an aberrant keratinocyte response to invading tumor cells, that could contribute to the formation of the typical ulcero-necrotic lesions within this entity.

Conclusions: Our scRNAseq profiling study reveals specific molecular patterns associated with distinct CTCL subtypes.

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CD4+、CD8+和TCR-γδ+皮肤T细胞淋巴瘤的单细胞RNA测序比较揭示了亚群特异性分子表型。

背景：原发性皮肤 T 细胞淋巴瘤（CTCL）的恶性克隆可表现为 CD4、CD8 或 TCR-γδ 表型，但它们对肿瘤生物学和皮损形成的个体影响仍不明确：对 CD4+ 与 CD8+ 和 TCR-γ/δ+ CTCL 病变进行全面的分子鉴定：我们对 18 例 CTCL 皮肤活检组织进行了 scRNA-seq，以比较典型 CD4+ 晚期真菌病（MF）与 TCR-γ/δ+MF 和原发性皮肤 CD8+ 侵袭性表皮细胞毒性 T 细胞淋巴瘤（Berti 淋巴瘤）：结果：TCR-γ/δ+MF和Berti淋巴瘤的恶性克隆显示出与CD4+MF不同的类似聚类模式，同时NKG7、CTSW、GZMA和GZMM等细胞毒性标志物的表达也有所增加。只有晚期CD4+MF克隆表达中枢记忆T细胞标记（SELL、CCR7、LEF1），同时有B1/B2血液参与，而TCR-γ/δ+MF和Berti淋巴瘤则有更多的组织驻留表型（CD69、CXCR4、NR4A1），血液中检测不到细胞。CD4+MF和TCR-γ/δ+MF皮肤病变的髓系细胞具有强烈的2型免疫激活，而Berti淋巴瘤则更偏向于1型免疫反应。CD4+MF 和 TCR-γ/δ+MF 病变都显示出角质细胞过度激活标志物（如 S100As 和 KRT16 基因）的上调。这种上调在伯蒂氏淋巴瘤中完全不存在，可能反映了角质细胞对入侵肿瘤细胞的异常反应，这可能是该实体形成典型溃疡-坏死性病变的原因之一：我们的 scRNAseq 图谱研究揭示了与不同 CTCL 亚型相关的特定分子模式。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

British Journal of Dermatology 医学-皮肤病学

CiteScore

16.30

自引率

3.90%

发文量

1062

审稿时长

2-4 weeks

期刊介绍： The British Journal of Dermatology (BJD) is committed to publishing the highest quality dermatological research. Through its publications, the journal seeks to advance the understanding, management, and treatment of skin diseases, ultimately aiming to improve patient outcomes.