Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment
Ruoyan Li, Johanna Strobl, Elizabeth Poyner, Aya Balbaa, Fereshteh Torabi, Pavel Mazin, Nana-Jane Chipampe, Emily Stephenson, Ciro Ramírez-Suástegi, Vijaya Baskar Mahalingam Shanmugiah, Louis Gardner, Bayanne Olabi, Rowen Coulthard, Rachel A. Botting, Nina Zila, Elena Prigmore, Nusayhah Hudaa Gopee, Marta A. Chroscik, Efpraxia Kritikaki, Justin Engelbert, Issac Goh, Hon Man Chan, Harriet F. Johnson, Jasmine Ellis, V. Rowe, Win Tun, Gary Reynolds, Dexin Yang, April 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, Dave Horsfall, Daniela Basurto-Lozada, 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
Abstract
Abstract Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (T H 2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II + fibroblasts and dendritic cells that can maintain T H 2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.