Interleukin 17 and peripheral IL-17-expressing T cells are negatively correlated with the overall survival of head and neck cancer patients.

Meng-Hua Lee,Chia-Rui Shen,Chun-Ta Liao,Joseph Tung-Chieh Chang,Ya-Shan Chen,Ming-Ling Kuo

doi:10.18632/oncotarget.23934

Abstract

The presence and clinical significance of interleukin (IL)-17 and IL-17-expressing cells have recently been studied in several types of cancer, but their correlation to tumor development remains controversial. Additionally, the contribution of peripheral IL-17-expressing cells to head and neck cancer (HNC) progression is still poorly understood. We collected peripheral blood from healthy donors and HNC patients to isolate PBMCs. The percentages of IL-17-expressing cells and the production of inflammatory cytokines in PBMCs were measured to determine their association with clinical outcomes and overall survival in HNC. We evaluated the effect and potential mechanism of IL-17 on human oral squamous carcinomas in vitro using exogenous IL-17 stimulation. In comparison to healthy donors, the PBMCs of HNC patients have a significant accumulation of IL-17-expressing T cells and their frequencies were positively correlated with the disease stage. A significantly higher production of PBMC IL-17, TGF-β and IL-21 and plasma VEGF-A were found in HNC patients. Importantly, the 5-years overall survival of HNC patients with a higher percentage of IL-17-expressing cells is significantly decreased. Furthermore, the addition of IL-17 appeared to promote human oral squamous carcinoma cell proliferation via the production of IL-6 and VEGF-A. Our findings suggest that IL-17 has the potential to mediate pro-tumor immunity in the HNC tumor microenvironment. Enhanced IL-17-expressing cells, including Th17 and Tc17 cells, in the peripheral blood could be a significant predictor of a poor prognosis for HNC patients.

Highlights

Head and neck cancer (HNC) is the sixth most common cancer worldwide and affects approximately 0.6 million patients per year [1]
To examine whether peripheral IL-17-expressing cells are associated with head and neck cancer (HNC) tumor progression, we first analyzed the frequency of IL-17+ cells, including the population of T cells in the peripheral blood, of patients with HNC
It is known that T cells are a www.impactjournals.com/oncotarget major source of IL-17 production in many inflammatory diseases [12]; we assessed the phenotype of CD4+IL-17+ (Th17) and CD8+IL-17+ (Tc17) cells in the peripheral blood mononuclear cells (PBMCs) of HNC patients

Summary

Introduction

Head and neck cancer (HNC) is the sixth most common cancer worldwide and affects approximately 0.6 million patients per year [1]. A better understanding of the immune status of cancer patients, the distribution and regulation of pro-oncogenic and cancer-related inflammatory cytokines, will improve the clinical outcomes of HNC patients and provide new immunomodulatory approaches for HNC treatment. It has been shown that CD8+ T cells (Tc17), γδ T cells and other innate immune cell populations, including macrophages and neutrophils, can produce IL-17 [11,12,13,14]. Cytokines, such as TGF-β, IL-6, IL-1β, and IL-21, have been shown to be crucial for human Th17 cells differentiation in vitro [12, 15]

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