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Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response

Abstract : Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T follicular helper cells. Herein, we show that EZH2 mutations initiate FL by attenuating GC B cell requirement for T cell help and driving slow expansion of GC centrocytes that become enmeshed with and dependent on FDCs. By impairing T cell help, mutant EZH2 prevents induction of proliferative MYC programs. Thus, EZH2 mutation fosters malignant transformation by epigenetically reprograming B cells to form an aberrant immunological niche that reflects characteristic features of human FLs, explaining how indolent tumors arise from GC B cells.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-02797079
Contributor : Laurent Jonchère <>
Submitted on : Friday, June 5, 2020 - 2:27:34 PM
Last modification on : Tuesday, September 1, 2020 - 10:04:52 AM

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Wendy Beguelin, Matt Teater, Cem Meydan, Kenneth B. Hoehn, Jude M. Phillip, et al.. Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response. Cancer Cell, Elsevier, 2020, 37 (5), pp.655-+. ⟨10.1016/j.ccell.2020.04.004⟩. ⟨hal-02797079⟩

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