Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact.
Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact.
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单核细胞/巨噬细胞和CD4 + T细胞所突显的胰腺癌炎症特征及其临床影响
DOI：
10.1111/cas.12663
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发表时间：
2015-06
期刊：
影响因子：
5.7
通讯作者：
Kaneko S
中科院分区：
文献类型：
--
作者：
Komura T;Sakai Y;Harada K;Kawaguchi K;Takabatake H;Kitagawa H;Wada T;Honda M;Ohta T;Nakanuma Y;Kaneko S
胰腺导管腺癌（PDAC）是最致命的恶性肿瘤之一，预后极差。本研究的目的是提供一个详细的了解PDAC的病理生理学鉴于宿主的免疫反应。我们采用免疫组化染色、细胞因子/趋化因子浓度测定、基因表达分析和流式细胞术检测PDAC患者的PDAC组织、血清和外周血细胞。PDAC组织被巨噬细胞浸润，特别是CD 33 + CD 163 + M2巨噬细胞和同时表达程序性细胞死亡-1（PD-1）的CD 4 + T细胞。PDAC患者血清中IL-6、IL-7、IL-15、单核细胞趋化蛋白-1和γ-干扰素诱导蛋白-1浓度显著升高。PDAC患者和健康志愿者的CD 14+单核细胞和CD 4 + T细胞的基因表达谱是可辨别的，差异表达的基因与活化的炎症有关。有趣的是，PD-I在PDAC患者的外周血CD 4 + T细胞中显著上调。相应地，PDAC患者外周血细胞中CD 4 +PD-1+ T细胞的频率增加，并且这种增加与化疗耐药性相关。总之，PDAC患者的PDAC组织和外周血细胞中的炎症状况都很突出，突出了单核细胞/巨噬细胞以及CD 4 + T细胞对临床预后的影响。我们使用PDAC组织、血清和外周血通过免疫组织化学染色、细胞因子/趋化因子测量、基因表达分析和流式细胞术检查PDAC患者的炎症特征。发现PDAC患者局部癌组织及外周血中的免疫介导细胞主要为单核/巨噬细胞和CD 4 + T细胞，其中涉及到化疗对PDAC预后有临床影响的重要亚群。
Pancreatic ductal adenocarcinoma (PDAC) is among the most fatal of malignancies with an extremely poor prognosis. The objectives of this study were to provide a detailed understanding of PDAC pathophysiology in view of the host immune response. We examined the PDAC tissues, sera, and peripheral blood cells of PDAC patients using immunohistochemical staining, the measurement of cytokine/chemokine concentrations, gene expression analysis, and flow cytometry. The PDAC tissues were infiltrated by macrophages, especially CD33+CD163+ M2 macrophages and CD4+ T cells that concomitantly express programmed cell death-1 (PD-1). Concentrations of interleukin (IL)-6, IL-7, IL-15, monocyte chemotactic protein-1, and interferon-γ-inducible protein-1 in the sera of PDAC patients were significantly elevated. The gene expression profile of CD14+ monocytes and CD4+ T cells was discernible between PDAC patients and healthy volunteers, and the differentially expressed genes were related to activated inflammation. Intriguingly, PD-1 was significantly upregulated in the peripheral blood CD4+ T cells of PDAC patients. Correspondingly, the frequency of CD4+PD-1+ T cells was increased in the peripheral blood cells of PDAC patients, and this increase correlated to chemotherapy resistance. In conclusion, inflammatory conditions in both PDAC tissue and peripheral blood cells in PDAC patients were prominent, highlighting monocytes/macrophages as well as CD4+ T cells with influence of the clinical prognosis. We examined the inflammatory features of PDAC patients using the PDAC tissues, sera, and peripheral blood by immunohistochemical staining, measurement of cytokines/chemokines, gene expression analysis, and flow cytometry. We foundg that monocyte/macrophage cells and CD4+ T cells were highlighted immune-mediating cells in local cancer tissue as well as in peripheral blood of PDAC patients, among which the important subfraction with clinical impact influencing PDAC prognosis by chemotherapy was involved.
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DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
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影响因子：
51.1
作者：
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通讯作者：
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影响因子：
2.8
作者：
Fabriek, BO;Dijkstra, CD;van den Berg, TK
通讯作者：
van den Berg, TK
影响因子：
32.4
作者：
Zhang N;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
11.2
作者：
Facciabene A;Motz GT;Coukos G
通讯作者：
Coukos G