Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer.

Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer.
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DOI:
10.1038/bjc.2013.32
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发表时间:
2013-03-05
影响因子:
8.8
通讯作者:
Hiraoka N
Hiraoka N
中科院分区:
医学1区
文献类型:
--
作者:
Ino Y;Yamazaki-Itoh R;Shimada K;Iwasaki M;Kosuge T;Kanai Y;Hiraoka N

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宿主免疫反应表现为免疫/炎性细胞浸润。在此我们系统地分析了胰腺导管癌(PDC)中肿瘤浸润的免疫/炎性细胞,并评估了它们对临床病理的影响。 我们利用免疫组织化学方法,检测了212例PDC中肿瘤浸润的CD68⁺泛巨噬细胞、HLA - DR⁺CD68⁺ M1型巨噬细胞(M1)、CD163⁺或CD204⁺ M2型巨噬细胞(M2)、CD66b⁺中性粒细胞(Neu)、CD4⁺T细胞(CD4⁺T)、CD8⁺T细胞(CD8⁺T)以及FOXP3⁺CD4⁺调节性T细胞(Treg),并使用卡普兰 - 迈耶方法和考克斯比例风险模型进行了相关性和生存分析。 肿瘤浸润的泛巨噬细胞、M2、Neu水平较高,或者调节性T细胞与CD4⁺T细胞的比率(%Treg)较高,均与较短的生存期显著相关,而肿瘤浸润的CD4⁺T、CD8⁺T水平较高,或者M1与泛巨噬细胞的比率(%M1)较高,则与较长的生存期显著相关。对这些变量两两进行生存分析显示,某些由此产生的患者组具有明显更长的生存期。然后我们将明显相关的因素联系起来,出现了两个重要变量:肿瘤浸润的CD4⁺T高/CD8⁺T高/%Treg低以及肿瘤浸润的%M1高/M2低。多变量生存分析表明,这些变量与较长的生存期显著相关,且具有较高的风险比。 肿瘤浸润的CD4⁺T高/CD8⁺T高/%Treg低以及%M1高/M2低是可用于评估PDC免疫微环境的独立预后因素。
The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact. Using immunohistochemistry, we examined tumour-infiltrating CD68+ pan-macrophages, HLA-DR+CD68+ M1 macrophages (M1), CD163+ or CD204+ M2 macrophages (M2), CD66b+ neutrophils (Neu), CD4+ T cells (CD4+T), CD8+ T cells (CD8+T), and FOXP3+CD4+ regulatory T cells (Treg) in 212 cases of PDC, and conducted correlation and survival analyses using the Kaplan–Meier method and Cox proportional hazards model. Higher levels of tumour-infiltrating pan-macrophages, M2, Neu, or the ratio of Tregs to CD4+T (%Treg) were significantly associated with shorter survival, whereas higher levels of tumour-infiltrating CD4+T, CD8+T, or the ratio of M1 to pan-macrophages (%M1) were significantly associated with longer survival. Survival analysis of pairs of these variables revealed that some of the resulting patient groups had exclusively longer survival. We then connected the apparently related factors, and two significant variables emerged: tumour-infiltrating CD4+Thigh/CD8+Thigh/%Treglow and tumour-infiltrating %M1high/M2low. Multivariate survival analysis revealed that these variables were significantly correlated with longer survival and had a higher hazard ratio. Tumour-infiltrating CD4+Thigh/CD8+Thigh/%Treglow and %M1high/M2low are independent prognosticators useful for evaluating the immune microenvironment of PDC.
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