Nature communications · 2022
Single-cell profiling reveals a memory B cell-like subtype of follicular lymphoma with increased transformation risk.
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Wang Xuehai, Nissen Michael, Gracias Deanne, Kusakabe Manabu, Simkin Guillermo, Jiang Aixiang, Duns Gerben, Sarkozy Clementine, Hilton Laura, Chavez Elizabeth A, Segat Gabriela C, Wong Rachel, Kim Jubin, Aoki Tomohiro, Islam Rashedul, May Christina, Hung Stacy, Tyshchenko Kate, Brinkman Ryan R, Hirst Martin, Karsan Aly, Freeman Ciara, Sehn Laurie H, Morin Ryan D, Roth Andrew J, Savage Kerry J, Craig Jeffrey W, Shah Sohrab P, Steidl Christian, Scott David W, Weng Andrew P
Аннотация
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.