Association between PD-L1 expression combined with tumor-infiltrating lymphocytes and the prognosis of patients with advanced hypopharyngeal squamous cell carcinoma.

Takeharu Ono,Fumihiko Sato,Buichiro Shin,Tetsuro Sasada,Satoshi Hattori,Koichi Azuma,Jun Akiba,Akihiko Kawahara,Umeno Hirohito,Shun-Ich Chitose

doi:10.18632/oncotarget.21564

Abstract

Limited information is available regarding the immune-related prognostic factors of patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC). The expression of programmed cell death-ligand 1 (PD-L1) in tumor cells contributes to a mechanism that allows cancer cells to escape immune surveillance. We investigated whether PD-L1 or human leukocyte antigen (HLA) class I expression in tumor cells and the tumor-infiltrating lymphocyte (TIL) density were associated with the tumor response to neoadjuvant chemotherapy (NAC) and survival in patients with advanced HPSCC. We retrospectively reviewed 83 consecutive patients with stage III or IV HPSCC who received NAC. We evaluated PD-L1 and HLA class I expression and TIL density using immunohistochemistry. Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for the response to NAC, progression-free survival (PFS) and overall survival (OS), whereas PD-L1 or HLA class I expression did not significantly correlate. The subgroup analysis revealed that a higher CD8+ TIL density without detectable PD-L1 expression tended to be associated with longer patient survival. These results suggest that PD-L1 expression levels combined with CD8+ TIL density may serve as a predictive biomarker for patients with stage III or IV HPSCC receiving NAC.

Highlights

Hypopharyngeal squamous cell carcinoma (HPSCC) accounts for 3%–5% of all head and neck squamous cell carcinoma (HNSCC) [1]
We investigated whether programmed cell death-ligand 1 (PD-L1) or human leukocyte antigen (HLA) class I expression in tumor cells and the tumor-infiltrating lymphocyte (TIL) density were associated with the tumor response to neoadjuvant chemotherapy (NAC) and survival in patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC)
These results suggest that progressive disease (PD)-L1 expression levels combined with CD8+ TIL density may serve as a predictive biomarker for patients with stage III or IV HPSCC receiving NAC

Summary

Introduction

Hypopharyngeal squamous cell carcinoma (HPSCC) accounts for 3%–5% of all head and neck squamous cell carcinoma (HNSCC) [1]. Most patients with HPSCC present with advanced disease and have the worst prognosis among those with HNSCCs arising from different anatomical sites, despite the development of treatments comprised of surgery and chemotherapy with or without radiotherapy [2]. The binding of PD-1 to its ligand, programmed cell deathligand 1, induces apoptosis or exhaustion in activated T cells, and inhibition of this interaction enhances the antitumor activity of T cells [10]. PD1 and PD-L1 are considered immune checkpoint molecules. Specific antibodies, which act as immune checkpoint blockers to inhibit the interactions between PD-1 and its ligands, PDL1 and PD-L2, exhibit promising clinical efficacy against certain malignancies [11,12,13]

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