Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer
Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer
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DOI：
10.1073/pnas.0611533104
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发表时间：
2007-02-27
影响因子：
11.1
通讯作者：
Fujii, Shingo
中科院分区：
文献类型：
--
作者：
Hamanishi, Junzo;Mandai, Masaki;Fujii, Shingo
程序性细胞死亡1（programmed cell death 1，PID-1）是一种免疫抑制性受体，属于CD 28/细胞毒性T淋巴细胞抗原4家族，其配体是PD-1配体1和2（PD-Ls）。近年来的研究表明，PD-Ls在肿瘤细胞上的异常表达损害了抗肿瘤免疫，导致肿瘤细胞的免疫逃避。虽然PD-Ls的表达水平和患者的预后之间的负相关性已被报道为几种恶性肿瘤，随访期是有限的，因为缺乏适用于石蜡包埋标本的抗体（Ab）。本研究制备了抗PD-1配体1（PID-1-11）的抗体，并利用石蜡包埋标本分析了PD-Ls在人卵巢癌中的表达水平。PD-L1高表达患者的预后显著差于低表达患者。虽然PD-1配体2表达较高的患者预后也较差，但差异无统计学意义。PD-L1表达与上皮内CD 8（+）T淋巴细胞计数呈显著负相关，表明肿瘤细胞上的PID-L1直接抑制抗肿瘤CD 8（+）T细胞。多因素分析显示肿瘤细胞PID-L1表达和上皮内CID 8 + T淋巴细胞计数是独立的预后因素。PD-1/ PD-L通路可能是恢复卵巢癌抗肿瘤免疫的良好靶点。
The ligands for programmed cell death 1 (PID-1), an immunoinhibitory 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 (PID-1-11) and analyzed the expression level of PD-Ls in human ovarian cancer using paraff in-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 PID-L1 on tumor cells directly suppresses antitumor CD8(+) T cells. Multivariate analysis showed the expression of PID-L1 on tumor cells and intraepithelial CID8+ 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.