IL-6 induced M1 type macrophage polarization increases radiosensitivity in HPV positive head and neck cancer.

Affiliation

Department of Otolaryngology, Head and Neck Surgery, Harbin Medical University Cancer Hospital, Harbin, China. Electronic address: [Email]

Abstract

Radiation is a crucial component of head and neck squamous cell carcinoma (HNSC) treatment. Human papillomavirus-positive (HPV+) HNSC is significantly more radiosensitive than HPV- HNSC, but the mechanism underlying this increased sensitivity is unknown. We investigated the possible involvement of macrophage subpopulations as key mediators of HNSC radiosensitivity linked to HPV status. We collected forty-one clinical HNSC specimens and determined HPV status and radiosensitivity of each sample. We investigated cytokine mediated induction of macrophage polarization by HPV+ and HPV- HNSC cells. Radiosensitive HNSC tissues exhibited greater numbers of infiltrating M1 macrophages than radioresistant tumor tissue samples. Moreover, M1 macrophage numbers were positively correlated with HNSC radiosensitivity. HPV+ and HPV- tumor cells induced macrophage polarization to M1 and M2 type, respectively. HPV+ HNSC cells secreted more IL-6 than HPV- cells. HPV promoted tumor cell secretion of IL-6, thereby increasing radiosensitivity through M1 polarization of macrophages. M1 macrophages represent an important tissue microenvironment factor with implications for HNSC treatment efficacy and may prove valuable as a biomarker of radiation sensitivity.

Keywords

HNSC,Human papillomavirus,Microenvironment,Radiotherapy,