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Follicular lymphoma triggers phenotypic and functional remodeling of the human lymphoid stromal cell landscape

2021; Cell Press; Volume: 54; Issue: 8 Linguagem: Inglês

10.1016/j.immuni.2021.05.019

1097-4180

Frédéric Mourcin, Léa Verdière, David Roulois, Rada Amin, Claire Lamaison, Vonick Sibut, Brice Thamphya, Céline Pangault, Céline Monvoisin, Sarah Huet, Marine Seffals, Sylvain Baulande, Fatima Mechta‐Grigoriou, Patricia Legoix, Delphine Rossille, Marion Guirriec, Simon Léonard, Guillaume Cartron, Gilles Salles, Thierry Fest, Karin Tarte,

Cancer Immunotherapy and Biomarkers

Summary Lymphoid stromal cells (LSCs) are essential organizers of immune responses. We analyzed tonsillar tissue by combining flow cytometry, in situ imaging, RNA sequencing, and functional assays, defining three distinct human LSC subsets. The integrin CD49a designated perivascular stromal cells exhibiting features of local committed LSC precursors and segregated cytokine and chemokine-producing fibroblastic reticular cells (FRCs) supporting B and T cell survival. The follicular dendritic cell transcriptional profile reflected active responses to B cell and non-B cell stimuli. We therefore examined the effect of B cell stimuli on LSCs in follicular lymphoma (FL). FL B cells interacted primarily with CD49a + FRCs. Transcriptional analyses revealed LSC reprogramming in situ downstream of the cytokines tumor necrosis factor (TNF) and transforming growth factor β (TGF-β), including increased expression of the chemokines CCL19 and CCL21. Our findings define human LSC populations in healthy tissue and reveal bidirectional crosstalk between LSCs and malignant B cells that may present a targetable axis in lymphoma.