TPF induction chemotherapy increases PD-L1 expression in tumour cells and immune cells in head and neck squamous cell carcinoma

Charlotte Leduc; Julien Adam; Emilie Louvet; Tony Sourisseau; Nicolas Dorvault; Marine Bernard; Elodie Maingot; Laura Faivre; Mei-Shiue Cassin-Kuo; Emilie Boissier; Marie-Charlotte Dessoliers; Angélique Robin; Odile Casiraghi; Caroline Even; Stéphane Temam; Ken A Olaussen; Jean-Charles Soria; Sophie Postel-Vinay

doi:10.1136/esmoopen-2017-000257

TPF induction chemotherapy increases PD-L1 expression in tumour cells and immune cells in head and neck squamous cell carcinoma

ESMO Open. 2018 Jan 9;3(1):e000257. doi: 10.1136/esmoopen-2017-000257. eCollection 2018.

Authors

Charlotte Leduc^{1

2

3

4

5

6}, Julien Adam^{1

2}, Emilie Louvet¹, Tony Sourisseau¹, Nicolas Dorvault¹, Marine Bernard¹, Elodie Maingot¹, Laura Faivre^{3

4}, Mei-Shiue Cassin-Kuo¹, Emilie Boissier¹, Marie-Charlotte Dessoliers¹, Angélique Robin¹, Odile Casiraghi², Caroline Even⁵, Stéphane Temam⁵, Ken A Olaussen¹, Jean-Charles Soria^{1

6}, Sophie Postel-Vinay^{1

6}

Affiliations

¹ INSERM, UMR981, F-94805, Villejuif, France, Paris Sud University, Gustave Roussy, Villejuif, France.
² Department of Pathology, Gustave Roussy, Villejuif, France.
³ Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France.
⁴ INSERM U1018, Paris Sud University, Gustave Roussy, Villejuif, France.
⁵ Department of Head and Neck Surgery, Gustave Roussy, Villejuif, France.
⁶ Drug development unit (DITEP), Gustave Roussy Cancer Campus, Paris-Saclay University, F-94805, Villejuif, France, Gustave Roussy, France.

Abstract

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.

Keywords: head and neck squamous cell carcinoma; immune checkpoint blockers; immunotherapy; induction chemotherapy; pd-l1.