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Oral Oncol. 2019 Apr;91:47-55. doi: 10.1016/j.oraloncology.2019.02.027. Epub 2019 Feb 28.

The prognosis of head and neck squamous cell carcinoma related to immunosuppressive tumor microenvironment regulated by IL-6 signaling.

Author information

1
Department of Otolaryngology & Head and Neck Surgery, Chang Gung Memorial Hospital at Chiayi, Taiwan; Chang Gung University College of Medicine, Taiwan.
2
Chang Gung University College of Medicine, Taiwan; Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan.
3
Department of Hematology and Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan.
4
Chang Gung University College of Medicine, Taiwan; Department of Radiation Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan. Electronic address: miaofen@adm.cgmh.org.tw.

Abstract

Evasion of immune surveillance is a significant factor in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. IL-6 signaling is a critical mechanism for the induction of dysfunctional immune responses. In the present study, we examined the role of IL-6 in the prognosis of HNSCC regarding the immunosuppressive tumor microenvironment. We retrospectively analyzed the clinical outcomes of HNSCC patients and examined its correlation with the levels of IL-6 in tumors and circulating myeloid-derived suppressor cells (MDSCs) in peripheral blood. Furthermore, the relationships between IL and 6, programmed death ligand (PD-L1) expression, and immune response were examined in vitro and in vivo. Our data revealed that IL-6 overexpression was associated with the increased risk of developing disease failure and poor prognosis for HNSCC. The immunoreactivity of IL-6 in HNSCC specimens was positively linked to the staining of PD-L1 and the level of circulating MDSCs. By cellular and animal experiments, there were augmented radiation-induced increases in the expression of PD-L1 and the activation of MDSCs noted in IL-6-positive tumors. When IL-6 signaling was inhibited, the levels of PD-L1 and MDSC recruitment were significantly down-regulated. Furthermore, the neutrophil-to-lymphocyte ratio (NLR) was positively correlated with the levels of IL-6 and PD-L1 in tumor, and circulating MDSCs. In conclusion, IL-6 is a significant predictor of treatment outcome in HNSCC patients, and plays an important role in the induction of immunosuppressive tumor microenvironment mediated by increased MDSCs and PD-L1 expression. Furthermore, IL-6 combined with NLR can assist the clinician to make an informed decision regarding treatment options.

KEYWORDS:

Head and neck cancer; IL-6; Immune; MDSC; PD-L1

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