PD-L1(+)MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment.
PD-L1(+)MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment.
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HCC患者的PD-L1（+）MDSC增加，并由肿瘤微环境中的可溶性因子诱导。
DOI：
10.1038/srep39296
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发表时间：
2016-12-14
影响因子：
4.6
通讯作者：
Shimosegawa T
中科院分区：
文献类型：
--
作者：
Iwata T;Kondo Y;Kimura O;Morosawa T;Fujisaka Y;Umetsu T;Kogure T;Inoue J;Nakagome Y;Shimosegawa T
髓系抑制细胞(MDSCs)在免疫调节中具有重要作用，在多种恶性肿瘤患者中均可诱导MDSCs。MDSCs在肝细胞癌患者中的免疫抑制作用尚不清楚。因此，我们试图分析MDSCs在肝细胞癌患者中的生物学意义。采用多色流式细胞术对不同条件下肝细胞癌患者的PD-L1+MDSCs进行定量。肝癌患者PBMC中PD-L1+MDSCs的比例显著高于健康人(p <； 0.001)。治疗后PD-L1+MDSCs百分率降低(p <； )，且治疗前PD-L1+MDSCs百分率与无瘤生存期呈负相关。在Transwell共培养系统中，我们将PBMC和几个肝癌细胞系共培养后，PD-L1+MDSCs的百分比显著高于对照组(p <； 0.05)。在强烈诱导PD-L1+MDSCs的细胞系中，M-CSF和VEGFA的表达较高。肝细胞癌患者外周血中PD-L1+MDSCs的百分率明显高于正常人，且治疗后PD-L1+MDSCs的百分率降低，提示我们有可能将PD-L1+MDSCs作为一种新的肝细胞癌标志物。
Myeloid-derived suppressor cells (MDSCs) could have important roles in immune regulation, and MDSCs can be induced in patients with various malignant tumors. The immune-suppressive functions of MDSCs in hepatocellular carcinoma (HCC) patients have not been clarified. Therefore, we tried to analyze the biological significance of MDSCs in HCC patients. We quantified PD-L1+MDSCs of HCC patients in various conditions by using multi-color flow cytometry analysis. PBMCs from HCC patients contained significantly higher percentages of PD-L1+MDSCs in comparison to those from healthy subjects (p < 0.001). The percentages of PD-L1+MDSCs were reduced by curative treatment for HCC (p < 0.05), and the percentages of PD-L1+MDSCs before treatment were inversely correlated with disease-free survival time. After we cocultivated PBMCs and several liver cancer cell lines in a transwell coculture system, the percentages of PD-L1+MDSCs were significantly increased compared with control (p < 0.05). The expression of M-CSF and VEGFA was higher in the cell lines that strongly induced PD-L1+MDSCs. Peripheral blood from HCC patients had significantly higher percentages of PD-L1+MDSCs in comparison to those of healthy subjects, and the percentages of PD-L1+MDSCs were reduced by HCC treatment, suggesting that we might use PD-L1+MDSCs as a new biomarker of HCC.
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影响因子：
2.9
作者：
Mittal S;El-Serag HB
通讯作者：
El-Serag HB
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
4.3
作者：
Kondo, Yasuteru;Kimura, Osamu;Shimosegawa, Tooru
通讯作者：
Shimosegawa, Tooru
影响因子：
13.5
作者：
Palmer, Daniel H.;Midgley, Rachel S.;Adams, David H.
通讯作者：
Adams, David H.
影响因子：
50.3
作者：
Bruix, J;Boix, L;Llovet, JM
通讯作者：
Llovet, JM