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Integrative Analysis of Cell Crosstalk within Follicular Lymphoma Cell Niche: Towards a Definition of the FL Supportive Synapse

Abstract : Follicular lymphoma (FL), the most frequent indolent non-Hodgkin's B cell lymphoma, is considered as a prototypical centrocyte-derived lymphoma, dependent on a specific microenvironment mimicking the normal germinal center (GC). In agreement, several FL genetic alterations affect the crosstalk between malignant B cells and surrounding cells, including stromal cells and follicular helper T cells (Tfh). In our study, we sought to deconvolute this complex FL supportive synapse by comparing the transcriptomic profiles of GC B cells, Tfh, and stromal cells, isolated from normal versus FL tissues, in order to identify tumor-specific pathways. In particular, we highlighted a high expression of <i>IL-6</i> and <i>IL-7</i> in FL B cells that could favor the activation of FL Tfh overexpressing IFNG, able in turn to stimulate FL B cells without triggering MHC (major histocompatibility) class II expression. Moreover, the glycoprotein clusterin was found up-regulated in FL stromal cells and could promote FL B cell adhesion. Finally, besides its expression on Tfh, CD200 was found overexpressed on tumor B cells and could contribute to the induction of the immunosuppressive enzyme indoleamine-2,3 dioxygenase by CD200R-expressing dendritic cells. Altogether our findings led us to outline the contribution of major signals provided by the FL microenvironment and their interactions with malignant FL B cells.
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Submitted on : Monday, October 26, 2020 - 3:48:39 PM
Last modification on : Wednesday, October 28, 2020 - 3:12:19 AM

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Céline Pangault, Patricia Amé-Thomas, Delphine Rossille, Joelle Dulong, Gersende Caron, et al.. Integrative Analysis of Cell Crosstalk within Follicular Lymphoma Cell Niche: Towards a Definition of the FL Supportive Synapse. Cancers, MDPI, 2020, 12 (10), pp.2865. ⟨10.3390/cancers12102865⟩. ⟨hal-02978621⟩

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