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 1, 2, 3 , Joseph Tung-Chieh Chang 4, 5, 6 , Chun-Ta Liao 4, 7 , Ya-Shan Chen 1, 3 , Ming-Ling Kuo 1, 2, 8, 10 and Chia-Rui Shen 1, 3, 9, 10 1 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 2 Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan 3 Department and Graduate Institute of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan 4 School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan 5 Department of Radiation Oncology, Lin-Kuo Chang Gung Memorial Hospital, Taoyuan, Taiwan 6 Department of Radiation Oncology, Xiamen Chang Gung Memorial Hospital, Xiamen, Fujian, China 7 Department of Otorhinolaryngology, Head and Neck Surgery, Lin-Kuo Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan 8 Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Lin-Kuo Chang Gung Memorial Hospital, Taoyuan, Taiwan 9 Department of Ophthalmology, Lin-Kuo Chang Gung Memorial Hospital, Taoyuan, Taiwan 10 Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taiwan Correspondence to: Chia-Rui Shen, email: crshen@mail.cgu.edu.tw Keywords: head and neck cancer; PBMCs; interleukin-17; Th17 cells; prognosis Received: June 05, 2017      Accepted: November 04, 2017      Published: January 03, 2018 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.