Single-cell Profiling Reveals a Memory B Cell-like Subtype of Follicular Lymphoma with Increased Transformation Risk

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Nov 9

PMID 36351924

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

Affiliations

Soon will be listed here.

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.

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