Programmed cell death ligand 1 (PD-L1), inducing T cells exhaustion to facilitate immune escape of tumor cells, is up-regulated 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 the 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<0.05), and multifocality, lymph node metastasis, distant metastasis, risk stratification and IL-6 expression were identified as the independent predictors of PD-L1 expression (p<0.05). The invasiveness of thyroid cancer was significantly enhanced after IL-6 treatment or PD-L1 overexpression. PD-L1 positive rate correlated with IL6 expression in cancer tissues (p<0.001). And after IL-6 treatment, the PD-L1 expression in TPC-1 and BCPAP significantly increased. MAPK and JAK-STAT3 signaling pathways were activated by IL-6. And the IL-6-induced PD-L1 expression decreased after treatment of 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. And IL-6 up-regulates PD-L1 expression through MAPK and JAK-STAT3 signaling pathway which function via transcription factors c-Jun and stat3.
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