IL‐6 expression promoted by Poly(I:C) in cervical cancer cells regulates cytokine expression and recruitment of macrophages

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 3; pp. 2284 - 2293
• Main Authors: Liu, Xin, Meng, Lihua, Chen, Ling, Liang, Ying, Wang, Bingyu, Shao, Qianqian, Wang, Huayang, Yang, Xingsheng
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-02-2020; John Wiley and Sons Inc
• Subjects: Antigens; Cancer vaccines; CCL22 protein; Cell Line; Cell Line, Tumor; Cervical cancer; cervical cancer cell; Cervix; Cytokines; Cytokines - metabolism; Dendritic cells; Experiments; Female; Fluorides; HeLa Cells; Human papillomavirus; Humans; IL‐6; Immune response; Inflammation; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Macrophages; Macrophages - drug effects; Macrophages - metabolism; NF-kappa B - metabolism; Original; Phosphorylation; Poly I-C - pharmacology; poly(I:C); Polyinosinic:polycytidylic acid; recruitment; Signal transduction; Signal Transduction - drug effects; siRNA; THP-1 Cells; Transcription; Transfection; Tumor cell lines; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumor necrosis factor-TNF; Tumors; Up-Regulation - drug effects; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - metabolism; Vaccines; cervical cancer cell; macrophages; recruitment; IL-6; poly(I:C)
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.14911

Poly(I:C) is a promising adjuvant for cancer treatment vaccines to enhance the host anti‐tumour immune response. However, the roles of poly(I:C) in the cervical cancer microenvironment and local immune reactions are not well understood. In this study, we investigated the roles of poly(I:C) in the cervical cancer. We analysed the cytokine transcription and secretion of cervical cancer cell lines and THP‐1–derived macrophages after poly(I:C) treatment, respectively. These results revealed that IL‐6 was significantly up‐regulated, and this up‐regulation was partly dose dependent. poly(I:C)‐stimulated supernatant of cervical cancer cells promoted M1‐type cytokine IL‐1β and IL‐6 expression of THP‐1–derived macrophages, but inhibited the expression of M2‐type cytokine, IL‐10 and CCL22. The recruitment of THP‐1–derived macrophages by poly(I:C)‐stimulated cervical cancer cell supernatant was also enhanced. Inhibition of IL‐6 expression in cervical cancer cells by siRNA transfection almost completely reversed the effects of poly(I:C) treatment. Finally, we found that phosphorylation of the NF‐κB signalling pathway in cervical cancer cells occurred quickly after poly(I:C) treatment. Moreover, the NF‐κB signalling pathway inhibitor PDTC significantly inhibited poly(I:C)‐induced IL‐6 expression. Taken together, these results suggest that poly(I:C) might regulate the effects of cervical cancer cells on tumour‐infiltrated macrophages, and subsequently promote a pro‐inflammatory tumour microenvironment.