Single-cell profiling reveals a memory B cell-like subtype of follicular lymphoma with increased transformation risk

• DOI: 10.1038/s41467-022-34408-0
• Publication Date: 2022-11-09T15:02:56Z
• Authors: Xuehai Wang; Michael Nissen; Deanne Gracias; Manabu Kusakabe; Guillermo Simkin; Aixiang Jiang; Gerben Duns; Clementine Sarkozy; Laura Hilton; Elizabeth A. Chavez; Gabriela C. Segat; Rachel Wong; Jubin Kim; Tomohiro Aoki; Rashedul Islam; Christina May; Stacy Hung; Kate Tyshchenko; Ryan R. Brinkman; Martin Hirst; Aly Karsan; Ciara Freeman; Laurie H. Sehn; Ryan D. Morin; Andrew J. Roth; Kerry J. Savage; Jeffrey W. Craig; Sohrab P. Shah; Christian Steidl; David W. Scott; Andrew P. Weng
• Keywords: B-Lymphocytes; 0303 health sciences; 03 medical and health sciences; Memory B Cells; Science; Q; Mutation; Humans; Germinal Center; Lymphoma, Follicular; Article; 3. Good health

AbstractFollicular lymphoma (FL) is an indolent cancer of mature B-cells but with ongoing risk of transformation to more aggressive histology over time. Recurrent mutations associated with transformation have been identified; however, prognostic features that can be discerned at diagnosis could be clinically useful. We present here comprehensive profiling of both tumor and immune compartments in 155 diagnostic FL biopsies at single-cell resolution by mass cytometry. This revealed a diversity of phenotypes but included two recurrent patterns, one which closely resembles germinal center B-cells (GCB) and another which appears more related to memory B-cells (MB). GCB-type tumors are enriched forEZH2,TNFRSF14, andMEF2Bmutations, while MB-type tumors contain increased follicular helper T-cells. MB-type and intratumoral phenotypic diversity are independently associated with increased risk of transformation, supporting biological relevance of these features. Notably, a reduced 26-marker panel retains sufficient information to allow phenotypic profiling of future cohorts by conventional flow cytometry.