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, 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 and Andrew P. Weng ()
Additional contact information
Xuehai Wang: BC Cancer Agency
Michael Nissen: BC Cancer Agency
Deanne Gracias: BC Cancer Agency
Manabu Kusakabe: BC Cancer Agency
Guillermo Simkin: BC Cancer Agency
Aixiang Jiang: BC Cancer Agency
Gerben Duns: BC Cancer Agency
Clementine Sarkozy: BC Cancer Agency
Laura Hilton: BC Cancer Agency
Elizabeth A. Chavez: BC Cancer Agency
Gabriela C. Segat: BC Cancer Agency
Rachel Wong: BC Cancer Agency
Jubin Kim: BC Cancer Agency
Tomohiro Aoki: BC Cancer Agency
Rashedul Islam: BC Cancer Agency
Christina May: BC Cancer Agency
Stacy Hung: BC Cancer Agency
Kate Tyshchenko: BC Cancer Agency
Ryan R. Brinkman: BC Cancer Agency
Martin Hirst: BC Cancer Agency
Aly Karsan: BC Cancer Agency
Ciara Freeman: BC Cancer Agency
Laurie H. Sehn: BC Cancer Agency
Ryan D. Morin: BC Cancer Agency
Andrew J. Roth: BC Cancer Agency
Kerry J. Savage: BC Cancer Agency
Jeffrey W. Craig: BC Cancer Agency
Sohrab P. Shah: BC Cancer Agency
Christian Steidl: BC Cancer Agency
David W. Scott: BC Cancer Agency
Andrew P. Weng: BC Cancer Agency

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34408-0

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