Patricia Amé-Thomas - T follicular helper cells in follicular lymphoma : one of the most important players in the malignant B cell niche

Follicular lymphoma (FL) is the most frequent indolent lymphoma and results from the malignant transformation of germinal centre B cells in secondary lymphoid organs. Beside the genetic alterations associated with the deregulation of the anti-apoptotic protein Bcl2, the growth of malignant FL B cells relies on the development of a supportive microenvironment, which forms a specialized cell niche contributing to disease development, progression, and drug resistance. Immunohistochemistry studies showed that malignant FL B cells are found admixed to specific stromal and immune cell subsets, in particular CD4⁺ T cells. In addition, some of these reports studying the expression of a unique T-cell marker revealed that more than their absolute number, the nature and the localization of T cells were associated with prognosis. This suggests that different functional CD4⁺ T cell subsets could play an important role in FL pathogenesis.Based on this hypothesis, we decided to explore by multi-color flow cytometry the CD4⁺ T cell compartment found in close contact with FL B cells in malignant lymph nodes.We demonstrated that CD4⁺ T cells localized in malignant follicles by their high expression of CXCR5 merged two distinct populations: a PD1⁺ ICOS⁺ CD25⁺ FOXP3⁺ T follicular regulatory cell subset (Tfr) and a PD1⁺ ICOS⁺ CD25^- FOXP3^- T follicular helper cell subset (Tfh). Using functional experiments on sorted T-cell subsets, we demonstrated that Tfr cells were able to inhibit the proliferation of effector T cells and were devoid of FL B-cell supportive effect. In addition, we revealed that tumor-infiltrating Tfh cells displayed a specific cytokine secretion profile, and had a supportive effect on malignant FL B cell growth. Finally, after a deeper characterization of this FL-Tfh compartment, we revealed that CD10⁺ FL-Tfh cells exhibited an IL-4^hi IFN-^low cytokine profile compared to their CD10^neg counterpart, associated with a better capacity to sustain malignant FL B-cell survival. Interestingly, we found that the specific stroma network was involved in the capacity of Tfh cells to highly synthetize IL-4. Overall, these observations revealed that CD4⁺ T cells in contact with malignant FL B cells have a more heterogeneous phenotype than previously assumed, and are fully involved in the maintenance of the tumor. These CD4⁺ T cell subsets emerge as a central therapeutic target, and evaluation of the proportion of these cells would be useful to better predict the biological effect of new drugs.

2^nd IGO meeting

La seconde édition des conférences organisées par le Labex IGO (IGO meeting) s’est déroulée les 21 et 22 avril 2016 à la Faculté de pharmacie de Nantes. Cette conférence a rassemblé 160 spécialistes de l’immunologie, de la transplantation et de l’oncologie. Des orateurs français et étrangers (USA, Grande-Bretagne, Pays-Bas, Espagne, Italie, Suisse) sont venus exposer leurs travaux et les dernières avancées dans leurs domaines de recherche. Des sessions (communications orales et posters) étaient également réservées aux jeunes chercheurs pour qu’ils puissent présenter leurs travaux et ainsi favoriser les échanges avec leurs collègues et les chercheurs séniors. Ce 2^nd IGO meeting, en créant un environnement propice à l’initiation de nouvelles collaborations à l’intérieur et au-delà du périmètre du Labex IGO, a été un vrai succès scientifique.