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Expression of STAT1 is positively correlated with PD-L1 in human ovarian cancer
Cancer Biology & Therapy ( IF 3.6 ) Pub Date : 2020-10-12 , DOI: 10.1080/15384047.2020.1824479
Fangran Liu 1, 2 , Jiao Liu 1 , Jinguo Zhang 1, 3 , Jimin Shi 1 , Lu Gui 2 , Guoxiong Xu 1, 3, 4
Affiliation  

ABSTRACT

Signal transducer and activator of transcription 1 (STAT1) is related to the immune microenvironment of tumorigenesis. The programmed cell death 1 (PD-1) and its ligand (PD-L1) have been reported to be important in immunotherapy by mediating tumor immune evasion. Blocking the PD-1/PD-L1 pathway can restore the endogenous anti-tumor immune response. This study aimed to examine the expression of STAT1, PD-1, and PD-L1 and the correlation between selected markers in human epithelial ovarian cancer (EOC). The results showed that malignant tumors contained more STAT1, PD-1, and PD-L1 positive cells. The expression of STAT1 and PD-L1 was associated with age, whereas PD-1 and PD-L1 associated with histopathological type, in patients with ovarian tumors. Moreover, the expression of STAT1 was found to be associated with disease stages and the grade of serous carcinoma. STAT1 expression was higher in OC cells than normal ovarian surface epithelial cells and was positively correlated with PD-L1 expression. The knockdown of STAT1 decreased PD-L1 expression, whereas overexpression of STAT1 increased PD-L1 expression. Furthermore, the expression of STAT1, PD-1, and PD-L1 was lower in paclitaxel-resistant cells than sensitive cells. Finally, STAT1 affected the overall survival and progression-free survival of patients with EOC. These findings suggest that STAT1, PD-1, and PD-L1 are the tissue markers of EOC and imply the possibility that the high level of STAT1, PD-1, and PD-L1 may favor the checkpoint immunotherapy in patients with EOC, but may have a limit in paclitaxel-resistant patients because of the low expression of STAT1, PD-1, and PD-L1 in paclitaxel-resistant cells.



中文翻译:

人卵巢癌中STAT1的表达与PD-L1呈正相关

摘要

信号转导和转录激活因子1(STAT1)与免疫微环境有关的肿瘤发生。据报道,程序性细胞死亡 1 (PD-1) 及其配体 (PD-L1) 通过介导肿瘤免疫逃避在免疫治疗中发挥重要作用。阻断PD-1/PD-L1通路可以恢复内源性抗肿瘤免疫反应。本研究旨在检查 STAT1、PD-1 和 PD-L1 的表达以及所选标志物在人上皮性卵巢癌 (EOC) 中的相关性。结果显示,恶性肿瘤含有较多的STAT1、PD-1和PD-L1阳性细胞。在卵巢肿瘤患者中,STAT1 和 PD-L1 的表达与年龄相关,而 PD-1 和 PD-L1 的表达与组织病理学类型相关。此外,发现STAT1的表达与疾病分期和浆液性癌的分级有关。OC 细胞中 STAT1 的表达高于正常卵巢表面上皮细胞,并与 PD-L1 表达呈正相关。STAT1 的敲低降低了 PD-L1 的表达,而 STAT1 的过表达增加了 PD-L1 的表达。此外,STAT1、PD-1 和 PD-L1 在紫杉醇耐药细胞中的表达低于敏感细胞。最后,STAT1 影响 EOC 患者的总生存期和无进展生存期。这些发现表明 STAT1、PD-1 和 PD-L1 是 EOC 的组织标志物,这意味着高水平的 STAT1、PD-1 和 PD-L1 可能有利于 EOC 患者的检查点免疫治疗,但由于 STAT1、PD-1 和 PD-L1 在紫杉醇耐药细胞中的低表达,因此在紫杉醇耐药患者中可能存在限制。

更新日期:2020-10-20
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