TY - JOUR
T1 - Ligand–receptor dissociated expression explains high TSLP without prognostic impact in human primary head and neck squamous cell carcinoma
AU - Guillot-Delost, Maude
AU - Guilleré, Lia
AU - Berger, Frédérique
AU - Ventre, Aurore
AU - Michea, Paula
AU - Sirven, Philémon
AU - Pattarini, Lucia
AU - Scholer-Dahirel, Alix
AU - Kebir, Fatima Zahra
AU - Huerre, Michel
AU - Chouchane-Mlik, Olfa
AU - Lappartient, Emmanuelle
AU - Rodriguez, José
AU - Jouffroy, Thomas
AU - Klijanienko, Jerzy
AU - Nicolas, André
AU - Sastre-Garau, Xavier
AU - Honorio, Sofia
AU - Mosseri, Véronique
AU - Le Peltier, Nelly
AU - Sablin, Marie Paule
AU - Le Tourneau, Christophe
AU - Tartour, Éric
AU - Badoual, Cécile
AU - Soumelis, Vassili
N1 - Publisher Copyright:
© 2016 Taylor & Francis Group, LLC.
PY - 2016/7/2
Y1 - 2016/7/2
N2 - 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.
AB - 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.
KW - Cytokines
KW - dendritic cells
KW - head and neck squamous cell carcinoma
KW - thymic stromal lymphopoietin
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=84978473767&partnerID=8YFLogxK
U2 - 10.1080/2162402X.2016.1179414
DO - 10.1080/2162402X.2016.1179414
M3 - Article
AN - SCOPUS:84978473767
SN - 2162-4011
VL - 5
JO - OncoImmunology
JF - OncoImmunology
IS - 7
M1 - e1179414
ER -