Authors: | Wang, X.; Nissen, M.; Gracias, D.; Kusakabe, M.; Simkin, G.; Jiang, A.; Duns, G.; Sarkozy, C.; Hilton, L.; Chavez, E. A.; Segat, G. C.; Wong, R.; Kim, J.; Aoki, T.; Islam, R.; May, C.; Hung, S.; Tyshchenko, K.; Brinkman, R. R.; Hirst, M.; Karsan, A.; Freeman, C.; Sehn, L. H.; Morin, R. D.; Roth, A. J.; Savage, K. J.; Craig, J. W.; Shah, S. P.; Steidl, C.; Scott, D. W.; Weng, A. P. |
Article Title: | Single-cell profiling reveals a memory B cell-like subtype of follicular lymphoma with increased transformation risk |
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. © 2022, The Author(s). |
Keywords: | controlled study; human tissue; gene mutation; human cell; major clinical study; genetics; mutation; cancer risk; cancer patient; flow cytometry; phenotype; cohort analysis; tumor biopsy; histology; b lymphocyte; b-lymphocytes; germinal center; memory; memory cell; malignant transformation; follicular lymphoma; lymphoma, follicular; lymph node biopsy; transformation; herpesvirus entry mediator; transcription factor ezh2; resolution; clinical outcome; diffuse large b cell lymphoma; cancer; humans; human; article; mass cytometry; tfh cell; single cell rna seq; memory b cells; memory b lymphocyte |
Journal Title: | Nature Communications |
Volume: | 13 |
ISSN: | 2041-1723 |
Publisher: | Nature Publishing Group |
Date Published: | 2022-11-09 |
Start Page: | 6772 |
Language: | English |
DOI: | 10.1038/s41467-022-34408-0 |
PUBMED: | 36351924 |
PROVIDER: | scopus |
PMCID: | PMC9646774 |
DOI/URL: | |
Notes: | Article -- Export Date: 1 December 2022 -- Source: Scopus |