Ligand–receptor dissociated expression explains high TSLP without prognostic impact in human primary head and neck squamous cell carcinoma

Maude Guillot-Delost, Lia Guilleré, Frédérique Berger, Aurore Ventre, Paula Michea, Philémon Sirven, Lucia Pattarini, Alix Scholer-Dahirel, Fatima Zahra Kebir, Michel Huerre, Olfa Chouchane-Mlik, Emmanuelle Lappartient, José Rodriguez, Thomas Jouffroy, Jerzy Klijanienko, André Nicolas, Xavier Sastre-Garau, Sofia Honorio, Véronique Mosseri, Nelly Le PeltierMarie Paule Sablin, Christophe Le Tourneau, Éric Tartour, Cécile Badoual, Vassili Soumelis

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

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Résumé

Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine expressed by epithelial cells during allergic inflammation, and activating dendritic cells (DC). Its expression and functional role in cancer remain controversial. We conducted retrospective (n = 89), and prospective studies including patients with untreated primary head and neck squamous cell carcinoma (HNSCC). We found that TSLP was overexpressed by HNSCC tumor cells, and associated with a highly differentiated status. However, no significant difference in overall and recurrence-free survival was found between patients bearing a tumor with high and low TSLP levels, respectively. Surprisingly, there was no significant association between the levels of TSLP expression, and the number of tumor-infiltrating mature DCLAMP+ DC. In order to explain the apparent lack of TSLP-induced DC activation, we performed phenotypic and functional experiments on freshly resected tumors. Tumor-infiltrating immune cells, including DC, did not express the TSLP receptor heterodimer (TSLPR chain, IL-7Ralpha chain). Furthermore, freshly sorted blood CD11c+ DC from healthy donors cultured with tumor-conditioned supernatant exhibited an activated profile, but this was not affected by an anti-TSLP blocking antibody, suggesting a DC activation pathway independent of tumor-derived TSLP. Overall, our results demonstrate that TSLP is overexpressed in HNSCC but its function is hampered by the lack of TSLPR-expressing cells in the tumor microenvironment. Such a dissociated ligand–receptor expression may impact intercellular communication in other immune activation pathways, and tumor types.

langue originaleAnglais
Numéro d'articlee1179414
journalOncoImmunology
Volume5
Numéro de publication7
Les DOIs
étatPublié - 2 juil. 2016
Modification externeOui

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