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Single-cell RNA sequencing comparison of CD4+, CD8+ and TCR-γδ+ cutaneous T-cell lymphomas reveals subset-specific molecular phenotypes.
Chennareddy, Sumanth; Rindler, Katharina; Ruggiero, John R; Alkon, Natalia; Cohenour, Emry R; Tran, Sophia; Weninger, Wolfgang; Griss, Johannes; Jonak, Constanze; Brunner, Patrick M.
Afiliación
  • Chennareddy S; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Rindler K; Department of Dermatology, Medical University of Vienna, Austria.
  • Ruggiero JR; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Alkon N; Department of Dermatology, Medical University of Vienna, Austria.
  • Cohenour ER; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Tran S; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Weninger W; Department of Dermatology, Medical University of Vienna, Austria.
  • Griss J; Department of Dermatology, Medical University of Vienna, Austria.
  • Jonak C; Department of Dermatology, Medical University of Vienna, Austria.
  • Brunner PM; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Br J Dermatol ; 2024 Aug 12.
Article en En | MEDLINE | ID: mdl-39133553
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Br J Dermatol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Br J Dermatol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido