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

Abstract

BackgroundAntiprogrammed 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 methodsPatients 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.ResultsOut 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.ConclusionTPF 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.

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

“…In particular, it has recently been shown that PD‐L1 significantly increased on residual disease after NACT compared with baseline in a large retrospective cohort of patients with TN early BC . The induction of PD‐L1 expression by chemotherapy is consistent with observations in other cancer types and with the notion that chemotherapy is able to induce an adaptive immune response through various mechanisms, including immunogenic cell death and the activation of the damage response c‐GAS/STING . Indeed, it has been shown that CT may boost the immunogenicity of the tumor by increasing tumor immune infiltrate from baseline to post‐NACT samples, with a high rate of conversion from low‐TIL to high‐TILs tumor .…”

“…It should also be noted that PD‐L1 stromal expression encompasses not only TILs but also macrophages and fibroblast‐like cells, thus further increasing the complexity of the biological role of PD‐L1 in possibly affecting response to immunotherapy .…”

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

“…PD-1 and PD-L1 expression currently remain the most significant tissue biomarkers. PD-L1 expression has been associated with postchemotherapy (docetaxel/platinum/5-fluorouracil regimen) status, 127 co-occurrence with p16 INK4 expression, 131 and poorer OS 124,126,128 (but improved RFS 125,129 and OS 125,130 ). Among these studies, associations between high PD-L1 expression and favorable OS were all demonstrated in post-surgery HNSCC patients.…”

Altered PD-L1 Expression in Non-Small Cell Lung Cancer Patient After Induction Chemotherapy: A Case Report

“…Neoadjuvant chemotherapy may up-regulate the expression of PD-L1 in lung squamous cell carcinoma as was recently published [15]. A recently published study showed increased PD-L1 expression on tumor cells in head and neck squamous cell carcinoma treated with TPF induction chemotherapy [16]. Another case report showed a decrease in PD-L1 level in NSCLC after chemotherapy including gemcitabine and platinum [17].…”