Résumés disponibles (92) :

RENAUD Sarah (UMR CNRS 8161 éq. 06 - Olivier MORALES)
Session :

 

@mail :  sarah.renaud@ibl.cnrs.fr      tél. :  0320871233


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Titre de la communication :
Induction of Tolerogenic Dendritic Cells using Nasopharyngeal Carcinoma-Derived Exosomes
Auteurs (et leurs adresses) de la communication :
Sarah RENAUD CNRS UMR 8161 groupe IRCV, Université de Lille, Institut Pasteur de Lille, Siric OncoLille, France
Résumé de la communication :
Background: A characteristic of the nasopharyngeal carcinoma (NPC) micro-environment is the presence of immunosuppressive exosomes released by tumor cells. Our team has recently shown that NPC-derived exosomes, which carry Galectine-9, favor the recruitment and suppressive activity of human regulatory T cells (Treg), thus contributing to NPC immune escape (Mrizak et al, JNCI, 2015). In this study, our objective is now to evaluate whether these NPC-derived exosomes could promote the emergence of tolerogenic immature dendritic cells (tolDC) able to induce regulatory T cells from naïve CD4+ T cells ultimately contributing to the tolerance of tumor cells.
Methods and Results: We performed a complete phenotypical and functional study comparing the effect of NPC and healthy donor-derived exosomes on DC maturation. This study includes (i) cell morphological analysis by photonic microscopy, (ii) transcriptomic study by RTqPCR, (iii) flow cytometric analysis of the expression of specific makers (phenotypic DC and Treg markers), (iv) a preliminary DC functional study by western blotting (IDO) and HPLC dosage of tryoptophan metabolites finally (v) a secretome analysis by ELISA (IL-10; TGF-β, TNF-α, IL-6 and IL-12). Taken together our results strongly suggest that the presence of NPC-derived exosomes favors the emergence of semi-mature DCs seemingly tolerogenic.
Conclusion: Despite the importance of immature DCs as mediators of cancer immune escape, no other studies have shown the impact of NPC tumor exosomes on the maturation of human DCs. Thus, these promising results should open new prospects for antitumor immunotherapies based on the inhibition of factors involved in the emergence and activation of Tregs.

RENAUD Sarah (UMR CNRS 8161 éq. 06 - Olivier MORALES)