PD-L1 expression patterns in tumour cells and their association with CD8+ tumour infiltrating lymphocytes in clear cell renal cell carcinoma

PD-L1 expression patterns in tumour cells and their association with CD8+ tumour infiltrating lymphocytes in clear cell renal cell carcinoma
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透明细胞肾细胞癌中肿瘤细胞中的 PD-L1 表达模式及其与 CD8 肿瘤浸润淋巴细胞的关联。

DOI:
10.7150/jca.29052
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发表时间:
2019-01-01
期刊:
影响因子:
3.9
通讯作者:
Xia, Jian-Chuan
Xia, Jian-Chuan
中科院分区:
医学3区
文献类型:
--
作者:
Zhu, Qian;Cai, Mu-Yan;Xia, Jian-Chuan

文献摘要

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目的:为探讨肾透明细胞癌(ccRCC)局部微环境中肿瘤细胞PD-L1(TC-PD-L1)的表达模式,材料与方法:选取30例新鲜原发性ccRCC组织,从mRNA水平检测TC-PD-L1与CD 8(+)TIL的相关性。体外孵育实验用于确认外源性TC-PD-L1表达与IFN γ之间的关联。2009年1月至2013年8月期间接受治疗的135例ccRCC患者的队列被纳入生存分析。结果:我们的结果证实,ccRCC细胞系能够表达PD-L1。体外孵育实验证实TC-PD-L1表达与干扰素-γ(IFN-γ)正相关。此外,对135例ccRCC患者进行生存分析,多因素分析发现TC-PD-L1表达与预后无独立相关性,而TC-PD-L1阳性ccRCC患者分为有或无CD 8(+)T细胞浸润时,其预后差异更明显。TC-PD-L1的高阳性率与CD 8(+)TILs的强浸润密切相关。具有大量CD 8(+)TIL浸润的TC-PD-L1阳性ccRCC患者赋予死亡和疾病复发的高风险。
Purpose: To evaluate the tumour cell PD-L1 (TC-PD-L1) expression patterns in the local microenvironment of clear cell renal cell carcinoma (ccRCC).Materials and Methods: 30 fresh primary ccRCC tissues were used to detect the association between TC-PD-L1 and CD8(+)TILs at mRNA level. The in vitro incubation experiment was used to confirm the association between extrinsic TC-PD-L1 expression and IFN gamma. A cohort of 135 ccRCC patients treated between January 2009 and August 2013 was included for survival analysis.Results: Our results confirmed that ccRCC cell lines were capable of expressing PD-L1. The incubation experiment in vitro demonstrated the positive correlation of TC-PD-L1 expression with interferon-gamma (IFN gamma). Additionally, survival analysis was investigated in 135 ccRCC patients and found no independent correlation of TC-PD-L1 expression in multivariate analysis, whereas more distinct prognostic differences were detected when TC-PD-L1-positive ccRCC were sub-classified as with or without CD8(+) T cell infiltration.Conclusion: The intrinsic and extrinsic expression patterns are both detected in ccRCC. High positive rate of TC-PD-L1 correlated closely to the strong infiltration of CD8(+) TILs. TC-PD-L1-positive ccRCC patients with abundant CD8(+) TILs infiltration confer the high risk of death and disease relapse.