Cutaneous T cell lymphoma atlas reveals malignant Th2 cells supported by a B cell-rich microenvironment

• DOI: 10.1101/2023.11.06.565474
• Publication Date: 2023-11-07T18:40:14Z
• Authors: Ruoyan Li; Johanna Strobl; Elizabeth F.M. Po...; Fereshteh Torabi; Pasha Mazin; Nana-Jane Chipampe; Emily Stephenson; Louis Gardner; Bayanne Olabi; Rowen Coulthard; Rachel A. Botting; Nina Zila; Elena Prigmore; Nusayhah Gopee; Justin Engelbert; Issac Goh; Hon Man Chan; Harriet Johnson; Jasmine Ellis; Victoria Rowe; Win Tun; Gary Reynolds; April Rose Foster; Laure Gambardella; Elena Winheim; Chloe Admane; Benjamin Rumney; Lloyd Steele; Laura Jardine; Julia Nenonen; Keir Pickard; Jennifer Lumley; Philip Hampton; Simeng Hu; Fengjie Liu; Xiangjun Liu; David Horsfall; Daniela Basurto-L...; Louise Grimble; Chris M. Bacon; Sophie Weatherhead; Hanna Brauner; Yang Wang; Fan Bai; Nick J. Reynolds; Judith E. Allen; Constanze Jonak; Patrick M. Brunner; Sarah A. Teichmann; Muzlifah Haniffa
• Keywords: Cutaneous T-cell lymphoma

Abstract Cutaneous T-cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form CTCL, mycosis fungoides (MF), can be difficult to diagnose resulting in treatment delay. pathogenesis CTCL not fully understood due limited data from patient studies. We performed single-cell RNA sequencing and spatial transcriptomics profiling skin patients with MF-type an integrated comparative analysis human cell atlas datasets healthy skin, atopic dermatitis psoriasis. reveal co-optation Th2-immune gene programmes by malignant modelling tumour microenvironment support their survival. identify MHC-II + fibroblast subsets reminiscent lymph node T-zone reticular monocyte-derived dendritic that maintain Th2-like cells. are spatially associated B cells, forming aggregates tertiary lymphoid structures which more prominent progressive disease. Finally, we validated enrichment infiltrates its association disease progression across three independent cohorts. Our findings provide diagnostic aids, potential biomarkers for staging therapeutic strategies CTCL.