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Lymphoma

Characterization of intratumoral follicular helper T cells in follicular lymphoma: role in the survival of malignant B cells

Abstract

Accumulating evidences indicate that the cellular and molecular microenvironment of follicular lymphoma (FL) has a key role in both lymphomagenesis and patient outcome. Malignant FL B cells are found admixed to specific stromal and immune cell subsets, in particular CD4pos T cells displaying phenotypic features of follicular helper T cells (TFH). The goal of our study was to functionally characterize intratumoral CD4pos T cells. We showed that CXCR5hiICOShiCD4pos T cells sorted from FL biopsies comprise at least two separate cell populations with distinct genetic and functional features: (i) CD25pos follicular regulatory T cells (TFR), and (ii) CD25neg TFH displaying a FL-B cell supportive activity without regulatory functions. Furthermore, despite their strong similarities with tonsil-derived TFH, purified FL-derived TFH displayed a specific gene expression profile including an overexpression of several genes potentially involved directly or indirectly in lymphomagenesis, in particular TNF, LTA, IL4 or CD40LG. Interestingly, we further demonstrated that these two last signals efficiently rescued malignant B cells from spontaneous and rituximab-induced apoptosis. Altogether, our study demonstrates that tumor-infiltrating CD4pos T cells are more heterogeneous than previously presumed, and underlines for the first time the crucial role of TFH in the complex set of cellular interactions within FL microenvironment.

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Acknowledgements

This work was supported by research funding from the Association pour la recherche sur le cancer (ARC AO 2007), the Institut National du Cancer (INCa translationnel 2010; PLBIO-10-195), and the Association pour le Développement de l’Hémato-Oncologie (ADHO). JLP was supported by a PhD studentship from the Association Leucémie Espoir. We are indebted to the Centre de Ressources Biologiques (CRB)-Santé of Rennes hospital for its support in the processing of biological samples, the Institut Fédératif de Recherche (IFR) 140 of Rennes for cell sorting core facility, and Christophe Ruaux for providing tonsil samples.

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Amé-Thomas, P., Le Priol, J., Yssel, H. et al. Characterization of intratumoral follicular helper T cells in follicular lymphoma: role in the survival of malignant B cells. Leukemia 26, 1053–1063 (2012). https://doi.org/10.1038/leu.2011.301

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