Single-cell profiling reveals a memory B cell-like subtype of follicular lymphoma with increased transformation risk
Xuehai Wang, Michael Nissen, Deanne Gracias, Manabu Kusakabe, G Simkin, Aixiang Jiang, Gerben Duns, Clémentine Sarkozy, Laura K. 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 L. Freeman, Laurie H. Sehn, Ryan D. Morin, Andrew Roth, Kerry J. Savage, Jeffrey W. Craig, Sohrab P. Shah, Christian Steidl, David W. Scott, Andrew P. Weng
Abstract
Follicular 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 for EZH2, TNFRSF14, and MEF2B mutations, 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.