Ligand-receptor dissociated expression explains high TSLP without prognostic impact in human primary head and neck squamous cell carcinoma.
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.
Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France; Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, Paris, France; Inserm Center of Clinical Investigation, CIC IGR Curie 1428, Paris, France.
Maude
M
Guillot-Delost
Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France; Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, Paris, France; Inserm Center of Clinical Investigation, CIC IGR Curie 1428, Paris, France.
Lia
L
Guilleré
Institut Curie, Service de biostatistiques , Paris, France.
Frédérique
F
Berger
Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France; Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, Paris, France; Inserm Center of Clinical Investigation, CIC IGR Curie 1428, Paris, France.
Aurore
A
Ventre
Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France; Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, Paris, France; Inserm Center of Clinical Investigation, CIC IGR Curie 1428, Paris, France.
Paula
P
Michea
Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France; Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, Paris, France; Inserm Center of Clinical Investigation, CIC IGR Curie 1428, Paris, France.
Philémon
P
Sirven
Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France; Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, Paris, France; Inserm Center of Clinical Investigation, CIC IGR Curie 1428, Paris, France.
Lucia
L
Pattarini
Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France; Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, Paris, France; Inserm Center of Clinical Investigation, CIC IGR Curie 1428, Paris, France.
Alix
A
Scholer-Dahirel
Institut Curie, Service de pathologie , Paris, France.
Fatima-Zahra
FZ
Kebir
Institut Curie, Service de pathologie , Paris, France.
Michel
M
Huerre
Institut Curie, Service de pathologie , Paris, France.
Olfa
O
Chouchane-Mlik
Institut Curie, Service de pathologie , Paris, France.
Emmanuelle
E
Lappartient
Institut Curie, Service de chirurgie , Paris, France.
José
J
Rodriguez
Institut Curie, Service de chirurgie , Paris, France.
Thomas
T
Jouffroy
Institut Curie, Service de pathologie , Paris, France.
Jerzy
J
Klijanienko
Institut Curie, Service de pathologie , Paris, France.
André
A
Nicolas
Institut Curie, Service de pathologie , Paris, France.
Xavier
X
Sastre-Garau
Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France; Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, Paris, France; Inserm Center of Clinical Investigation, CIC IGR Curie 1428, Paris, France.
Sofia
S
Honorio
Institut Curie, Service de biostatistiques , Paris, France.
Véronique
V
Mosseri
Institut Curie, Service de biostatistiques , Paris, France.
Nelly
N
Le Peltier
Institut Curie, Service d'oncologie , Paris, France.
Marie-Paule
MP
Sablin
Institut Curie, Service d'oncologie , Paris, France.
Christophe
C
Le Tourneau
Inserm U970 Immunothérapie et traitement anti-angiogénique en cancérologie, Université Paris Descartes, PARCC/HEGP , Paris, France.
Éric
É
Tartour
Inserm U970 Immunothérapie et traitement anti-angiogénique en cancérologie, Université Paris Descartes, PARCC/HEGP , Paris, France.
Cécile
C
Badoual
Institut Curie, Laboratoire d'Immunologie Clinique, Paris, France; Institut National de la Santé et de la Recherche Médicale, U932, Institut Curie, Paris, France; Inserm Center of Clinical Investigation, CIC IGR Curie 1428, Paris, France.
Vassili
V
Soumelis
Cytokines; dendritic cells; head and neck squamous cell carcinoma; thymic stromal lymphopoietin; tumor microenvironment