Abstract

Virus-associated malignancies and sarcomatoid cancers correlate with high PD-L1 expression, however, underlying mechanisms remain controversial. We evaluated the correlation between PD-L1 expression and epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinomas (HNSCC). Tumor tissues from 50 patients with HNSCC were evaluated for PD-L1 by immunohistochemistry, which showed 32 (64.0%) were PD-L1 positive (PD-L1+). Interestingly, PD-L1 expression was significantly associated with EMT (P = 0.010), as assessed by low E-cadherin and high vimentin expression. The overall survival of PD-L1+ patients with EMT features was significantly worse than those without EMT features (P = 0.007). In an independent validation cohort (N = 91), as well as in HNSCC cases of The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia, high PD-L1 expression was also associated with the high probability of an EMT signature, referred from the GEO dataset, GSE4824. Survival analysis confirmed PD-L1+/EMT+ patients had a poorer prognosis than PD-L1+/EMT- patients in the TCGA cohort. PD-L1 positivity can thus be divided into two categories according to the absence or presence of EMT. PD-L1 expression is also independently associated with EMT features in HNSCC.

Highlights

  • Discovery of programmed death-ligand 1 (PD-L1) expression in tumors has encouraged research toward more efficient immunologic methods of conquering cancer [1]

  • We evaluated the correlation between PD-L1 expression and epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinomas (HNSCC).Tumor tissues from 50 patients with HNSCC were evaluated for PD-L1 by immunohistochemistry, which showed 32 (64.0%) were PD-L1 positive (PD-L1+)

  • PD-L1 positivity was not significantly different according to p16 status (P = 0.199; Supplementary Figure 2A), PD-L1 positivity was significantly higher in p16-/EMT+ and p16+/EMTcompared with p16-/EMT- patients (P = 0.002 and 0.026, respectively; Supplementary Figure 2B)

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Summary

Introduction

Discovery of programmed death-ligand 1 (PD-L1) expression in tumors has encouraged research toward more efficient immunologic methods of conquering cancer [1]. Cancer cells have developed various strategies for evading host anti-cancer immunologic attacks, including the up-regulation of PD-L1, which induces T cell anergy and apoptosis by interacting with programmed death-1 (PD-1) receptors [2, 3]. Viruses and epithelial-mesenchymal transition (EMT) are associated with high PD-L1 expression [9]. PD-L1 up-regulation may occur in response to the constitutional up-regulation of CD274 gene amplification at 9p24.1, which encodes PD-L1 [10]. Another possible mechanism is PD-L1 induction by interferon-gamma secreted from tumor-infiltrating immune cells via the JAK/STAT pathway [12,13,14,15,16]. A comprehensive analysis of the association of PD-L1 with viruses and EMT has not yet been reported

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