TY - JOUR
T1 - TPF induction chemotherapy increases PD-L1 expression in tumour cells and immune cells in head and neck squamous cell carcinoma
AU - Leduc, Charlotte
AU - Adam, Julien
AU - Louvet, Emilie
AU - Sourisseau, Tony
AU - Dorvault, Nicolas
AU - Bernard, Marine
AU - Maingot, Elodie
AU - Faivre, Laura
AU - Cassin-Kuo, Mei Shiue
AU - Boissier, Emilie
AU - Dessoliers, Marie Charlotte
AU - Robin, Angélique
AU - Casiraghi, Odile
AU - Even, Caroline
AU - Temam, Stéphane
AU - Olaussen, Ken A.
AU - Soria, Jean Charles
AU - Postel-Vinay, Sophie
N1 - Publisher Copyright:
© European Society for Medical Oncology (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background Antiprogrammed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) therapies have demonstrated promising activity in advanced head and neck squamous cell carcinoma (HNSCC), with overall response rates of approximately 20% in unselected populations and survival benefit. Whether induction docetaxel, platinum and fluorouracil (TPF) modifies PD-L1 expression or tumour immune infiltrates is unknown. Patients and methods Patients with locally advanced HNSCC treated at Gustave Roussy (Villejuif, France) between 2006 and 2013 by induction TPF followed by surgery were retrospectively considered. Patients with paired samples (pre-TPF and post-TPF) were kept for further analysis. PD-L1 expression was quantified by immunohistochemistry according to a validated protocol. The objective of the study was to compare PD-L1 expression on tumour cells (TC) and immune cells (IC) (positivity threshold of ≥5%) before and after TPF. CD8+ and Foxp3+ lymphocytes densities before and after TPF were also quantified. Results Out of 313 patients receiving induction TPF, 86 underwent surgery; paired samples were available for 21 of them. Baseline PD-L1 expression was ≥5% in two and five samples for TC and IC, respectively. A significant increase of PD-L1 expression was observed after TPF, with 15 samples (71%) presenting a positive staining in IC after induction chemotherapy (P=0.003; Wilcoxon rank-sum test) and eight samples (38%) in TC (P=0.005; Wilcoxon rank-sum test). Tumour-infiltrating CD8+ mean densities also significantly increased post-TPF (P=0.01). There was no significant difference in Foxp3+ expression, CD8/Foxp3 ratio or correlation with outcome. Conclusion TPF induction chemotherapy in advanced HNSCC increases PD-L1 positivity on tumour-infiltrating ICs, as well as CD8+ lymphocytes density. These results warrant independent validation on larger datasets and might help therapeutic strategy in advanced HNSCC.
AB - Background Antiprogrammed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) therapies have demonstrated promising activity in advanced head and neck squamous cell carcinoma (HNSCC), with overall response rates of approximately 20% in unselected populations and survival benefit. Whether induction docetaxel, platinum and fluorouracil (TPF) modifies PD-L1 expression or tumour immune infiltrates is unknown. Patients and methods Patients with locally advanced HNSCC treated at Gustave Roussy (Villejuif, France) between 2006 and 2013 by induction TPF followed by surgery were retrospectively considered. Patients with paired samples (pre-TPF and post-TPF) were kept for further analysis. PD-L1 expression was quantified by immunohistochemistry according to a validated protocol. The objective of the study was to compare PD-L1 expression on tumour cells (TC) and immune cells (IC) (positivity threshold of ≥5%) before and after TPF. CD8+ and Foxp3+ lymphocytes densities before and after TPF were also quantified. Results Out of 313 patients receiving induction TPF, 86 underwent surgery; paired samples were available for 21 of them. Baseline PD-L1 expression was ≥5% in two and five samples for TC and IC, respectively. A significant increase of PD-L1 expression was observed after TPF, with 15 samples (71%) presenting a positive staining in IC after induction chemotherapy (P=0.003; Wilcoxon rank-sum test) and eight samples (38%) in TC (P=0.005; Wilcoxon rank-sum test). Tumour-infiltrating CD8+ mean densities also significantly increased post-TPF (P=0.01). There was no significant difference in Foxp3+ expression, CD8/Foxp3 ratio or correlation with outcome. Conclusion TPF induction chemotherapy in advanced HNSCC increases PD-L1 positivity on tumour-infiltrating ICs, as well as CD8+ lymphocytes density. These results warrant independent validation on larger datasets and might help therapeutic strategy in advanced HNSCC.
KW - head and neck squamous cell carcinoma
KW - immune checkpoint blockers
KW - immunotherapy
KW - induction chemotherapy
KW - pd-l1
UR - http://www.scopus.com/inward/record.url?scp=85048114318&partnerID=8YFLogxK
U2 - 10.1136/esmoopen-2017-000257
DO - 10.1136/esmoopen-2017-000257
M3 - Article
AN - SCOPUS:85048114318
SN - 2059-7029
VL - 3
JO - ESMO Open
JF - ESMO Open
IS - 1
M1 - e000257
ER -