1. Academic Validation
  2. Interleukin 6 regulates the expression of programmed cell death ligand 1 in thyroid cancer

Interleukin 6 regulates the expression of programmed cell death ligand 1 in thyroid cancer

  • Cancer Sci. 2021 Mar;112(3):997-1010. doi: 10.1111/cas.14752.
Guo-Qiang Zhang 1 Qiong Jiao 2 Chen-Tian Shen 1 Hong-Jun Song 1 Hui-Zhen Zhang 2 Zhong-Ling Qiu 1 Quan-Yong Luo 1
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  • 2 Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Abstract

Programmed cell death ligand 1 (PD-L1), inducing T cell exhaustion to facilitate immune escape of tumor cells, is upregulated by interleukin 6 (IL-6) in T cell lymphoma and ovarian Cancer. The purpose of this study is to investigate the expression of IL-6 and PD-L1 in thyroid Cancer, and whether IL-6 regulates PD-L1 expression. As a result, IL-6 and PD-L1 were highly expressed in thyroid Cancer tissues. Multivariate logistic analysis showed that tumor size, distant metastasis, and risk stratification were significantly associated with IL-6 expression (P < .05), and multifocality, lymph node metastasis, distant metastasis, risk stratification, and IL-6 expression were identified as the independent predictors of PD-L1 expression (P < .05). The invasiveness of thyroid Cancer was significantly enhanced after IL-6 treatment or PD-L1 overexpression. PD-L1 positive rate correlated with IL-6 expression in Cancer tissues (P < .001), and after IL-6 treatment, the PD-L1 expression in TPC-1 and BCPAP significantly increased. The mitogen-activated protein kinase pathway (MAPK) and the Janus-activated kinase (JAK)-signal transducers and activators of transcription 3 (STAT3) signaling pathways were activated by IL-6, and the IL-6-induced PD-L1 expression decreased after treatment with these two signaling pathway inhibitors. Knockdown of transcription factors c-Jun and STAT3 suppressed the expression of PD-L1 induced by IL-6, and these two factors could bind to PD-L1 gene promoter directly and promote its transcription. It is concluded that IL-6 and PD-L1 are overexpressed in thyroid Cancer and are related to tumor invasiveness. IL-6 upregulates PD-L1 expression through the MAPK and JAK-STAT3 signaling pathways, which function via transcription factors c-Jun and STAT3.

Keywords

IL-6; PD-L1; mechanism; regulation; thyroid cancer.

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