Intratumoral plasmacytoid dendritic cells as a poor prognostic factor for hepatocellular carcinoma following curative resection
Intratumoral plasmacytoid dendritic cells as a poor prognostic factor for hepatocellular carcinoma following curative resection
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瘤内浆细胞样树突状细胞是治愈性切除后肝细胞癌的不良预后因素
DOI：
10.1007/s00262-019-02355-3
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发表时间：
2019-08-01
影响因子：
5.8
通讯作者：
Zhou, Shao-Lai
中科院分区：
文献类型：
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作者：
Zhou, Zheng-Jun;Xin, Hao-Yang;Zhou, Shao-Lai
浆细胞样树突状细胞（pDCs）存在于各种原发性和转移性人类肿瘤中；然而，它们在肝细胞癌（HCC）中的临床意义尚不清楚。在本研究中，我们研究了行根治性切除的HCC患者中pDCs的分布、预后价值和潜在功能。我们对224例患者的全肿瘤切片进行了免疫组织化学分析，以评估BDCA2、CD3、CD4、CD8、Foxp3、颗粒酶B、IL-17和CD34的表达。另外两个独立队列共841例接受根治性切除的HCC患者的组织微阵列验证了这一发现。我们的研究结果表明，肿瘤内高数量的BDCA2+pDCs与高甲胎蛋白水平、更大的血管侵犯、更晚的肿瘤淋巴结转移阶段、更短的总生存期和更高的复发率相关。然而，患者的预后与肿瘤周围间质或非肿瘤组织中的pDCs无关。此外，肿瘤内pDCs的增加与肿瘤内Foxp3+调节性T细胞和il -17产生细胞的浸润增加有关，并与肿瘤血管密度相关。单因素和多因素分析显示，肿瘤内pDCs单独存在或与调节性T和/或产生il -17的细胞联合存在是复发时间和总生存期的独立预测因子。总之，我们的研究表明，肿瘤内pDCs浸润是HCC患者预后不良的一个新指标，可能是通过诱导由调节性T和il -17产生细胞组成的免疫耐受性和炎症性肿瘤微环境。对这些细胞组合的评估代表了对患者预后的优越预测。
Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in hepatocellular carcinoma (HCC) is unclear. In this study, we investigated the distribution, prognostic value, and potential function of pDCs in HCC patients undergoing curative resection. We performed immunohistochemical analyses of whole tumor sections from 224 patients to assess the expression of BDCA2, CD3, CD4, CD8, Foxp3, granzyme B, IL-17, and CD34. The findings were validated using tissue microarrays from another two independent cohorts totaling 841 HCC patients undergoing curative resection. Our results demonstrated that high numbers of BDCA2+pDCs within tumors correlated with high alpha-fetoprotein levels, greater vascular invasion, advanced tumor-node-metastasis stage, shorter overall survival, and a higher recurrence rate. However, patient outcomes were not associated with pDCs in peritumoral stromal or nontumor tissues. Furthermore, an increase in intratumoral pDCs was associated with increased intratumoral infiltration of Foxp3+regulatory T cells and IL-17-producing cells and correlated with tumor vascular density. Univariate and multivariate analyses revealed that the presence of intratumoral pDCs alone or in combination with regulatory T and/or IL-17-producing cells was an independent predictor of time to recurrence and overall survival. In conclusion, our study demonstrated that intratumoral infiltration by pDCs is a novel indicator for poor prognosis in patients with HCC, possibly through the induction of an immune tolerogenic and inflammatory tumor microenvironment comprising regulatory T and IL-17-producing cells. An assessment of the combination of these cells represents a superior predictor of patient outcome.