Mapping malignant T-cell states and immune circuits in Sézary syndrome by single-cell analysis - PubMed
8 hours ago
- #Sézary syndrome
- #single-cell RNA sequencing
- #cutaneous T-cell lymphoma
- Sézary syndrome (SS) and leukaemic mycosis fungoides (MF) are aggressive cutaneous T-cell lymphomas (CTCLs) with poor prognosis and limited treatment options.
- Single-cell RNA sequencing (scRNA-seq) was used to analyze 144,321 peripheral blood mononuclear cells from 22 patients (SS or leukaemic MF) and 7 healthy controls.
- Three transcriptionally distinct malignant T-cell (MTC) subtypes were identified: central memory-like (MTC CM), effector/effector memory-like (MTC E/EM), and regulatory-like (MTC Reg).
- MTC CM expressed central memory markers, Th2/Th22 skewing, and a broader KIR repertoire (KIR3DL2, KIR3DL1, KIR2DL3).
- MTC E/EM and MTC Reg were enriched for NR4A1 and ITGB1, respectively.
- Cell-cell communication analysis revealed KIR-MHC-I signalling and suggested that MTC-derived TNF and IL-10 may drive JAK/STAT pathway activity in non-T cells.
- The study provides insights into immune evasion mechanisms and potential therapeutic targets for SS and leukaemic MF.