Tumor Associated Macrophage (TAM) Derived IL-6 Induced Re-localization of PD-L1 in Ovarian Cancer Ce

来源 :第十三届全国肿瘤生物治疗学术会议 | 被引量 : 0次 | 上传用户:troy003
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  Objective: PD-L1 (also termed B7-H1) has been described to exert coinhibitory and immune regulatory functions.This study was to investigate the effect of tumor-associated macrophage on the PD-L1 expression on ovarian tumor cells.Methods: PD-L1 expression and CD68 cell infiltration in the ovarian carcinoma specimens was determinated by immunohistochemical staining.RT-PCR and FCM was used to detect the PD-L1 expression in culturing and primary ovarian cancer cell.To elucidate the functional significance of cancer-related PD-L1 expression, we performed co-culture experiments of cancer cell with CD68+ T cells.Results: In vivo, ovarian carcinoma lesions expressed PD-L1 protein weakly or intensely, which related to infiltrating degree of CD68+ cell.In vitro, although ovarian cancer line (SKOV3) constitutively expressed PD-L1 mRNA and protein in cytoplasm, PD-L1 was not expressed on the surface.In SKOV3 cell transplanted ovarian carcinoma model, the expression of membrane-bound PD-L1 on primary tumor cells was increased.Exposure to tumor-associated macrophage (TAM) also strongly induced membrane-bound PD-L1 expression on SK OV3, which was mediated though IL-6 produced by TAM but not autocrine IL-6 released from cancer cell.Ovarian cancerrelated PD-L1 was identified as a strong inhibitor of T-cell effect.Conclusions:TAM induced membrane-bound PD-L1 on the ovarian cancer cell represents a novel mechanism by which cancer cells evaded immune destruction.
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