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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Programmed cell death 1 ligand 1 and tumor- infiltrating CD8~+ T lymphocytes are prognostic factors of human ovarian cancer
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Programmed cell death 1 ligand 1 and tumor- infiltrating CD8~+ T lymphocytes are prognostic factors of human ovarian cancer

机译：程序性细胞死亡1配体1和肿瘤浸润的CD8〜+ T淋巴细胞是人卵巢癌的预后因素

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摘要

The ligands for programmed cell death 1 (PD-1), an immunoinhibi-tory receptor belonging to CD28/cytotoxic T lymphocyte antigen 4 family, are PD-1 ligand 1 and 2 (PD-Ls). Recent reports suggest that the aberrant expression of PD-Ls on tumor cells impairs antitumor immunity, resulting in the immune evasion of the tumor cells. Although an inverse correlation between the expression level of PD-Ls and patients' prognosis has been reported for several malignant tumors, the follow-up period was limited because of the lack of the antibody (Ab) applicable to paraffin-embedded specimens. Here we generated a new Ab against PD-1 ligand 1 (PD-L1) and analyzed the expression level of PD-Ls in human ovarian cancer using paraffin-embedded specimens. Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression. Although patients with higher expression of PD-1 ligand 2 also had a poorer prognosis, the difference was not statistically significant. A significant inverse correlation was observed between PD-L1 expression and the intraepithelial CD8~+ T lymphocyte count, suggesting that PD-L1 on tumor cells directly suppresses antitumor CD8~+ T cells. Multivariate analysis showed the expression of PD-L1 on tumor cells and intraepithelial CD8~+ T lymphocyte count are independent prognostic factors. The PD-1/ PD-L pathway can be a good target for restoring antitumor immunity in ovarian cancer.
机译：程序性细胞死亡1（PD-1）的配体是PD-1配体1和2（PD-Ls），PD-1是CD28 /细胞毒性T淋巴细胞抗原4家族的一种免疫抑制受体。最近的报道表明，PD-Ls在肿瘤细胞上的异常表达损害了抗肿瘤免疫力，导致肿瘤细胞的免疫逃避。尽管已经报道了几种恶性肿瘤PD-Ls的表达水平与患者预后之间呈负相关，但由于缺乏适用于石蜡包埋标本的抗体（Ab），因此随访时间有限。在这里，我们生成了针对PD-1配体1（PD-L1）的新抗体，并使用石蜡包埋的标本分析了PD-Ls在人卵巢癌中的表达水平。 PD-L1高表达的患者的预后明显低于低表达的患者。尽管PD-1配体2表达较高的患者预后较差，但差异无统计学意义。观察到PD-L1表达与上皮内CD8〜+ T淋巴细胞计数之间存在显着的负相关，表明肿瘤细胞上的PD-L1直接抑制了抗肿瘤CD8〜+ T细胞。多因素分析显示PD-L1在肿瘤细胞中的表达和上皮内CD8〜+ T淋巴细胞计数是独立的预后因素。 PD-1 / PD-L途径可能是恢复卵巢癌抗肿瘤免疫力的良好靶标。

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