High CD204+ tumor-infiltrating macrophage density predicts a poor prognosis in patients with urothelial cell carcinoma of the bladder.
High CD204+ tumor-infiltrating macrophage density predicts a poor prognosis in patients with urothelial cell carcinoma of the bladder.
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高 CD204 肿瘤浸润巨噬细胞密度预示膀胱尿路上皮细胞癌患者预后不良
DOI：
10.18632/oncotarget.3887
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发表时间：
2015-08-21
期刊：
影响因子：
--
通讯作者：
Lin T
中科院分区：
文献类型：
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作者：
Wang B;Liu H;Dong X;Wu S;Zeng H;Liu Z;Wan D;Dong W;He W;Chen X;Zheng L;Huang J;Lin T
巨噬细胞（Mφs）是一种主要的细胞类型，可以浸润实体瘤并在不同的肿瘤微环境中表现出不同的表型。本研究旨在探讨不同肿瘤浸润性Mφ表型对膀胱尿路上皮细胞癌（UCB）患者预后的价值，重点是Mφ组织微定位。采用免疫组织化学方法，以CD 68作为泛M φ标记物，CD 204和CD 169分别作为强有力的促肿瘤和抗肿瘤Mφ表型标记物，对302例UCB患者组织中的Mφ进行了评估。我们的数据表明，这些Mφ表型主要分布在间质（ST）而不是肿瘤内（INT）区域（均P < 0.0001）。令人惊讶的是，CD 204和CD 169可以由相同的CD 68 + Mφ共表达。Kaplan-Meier分析显示所有INT和ST浸润的CD 204+或CD 169 + Mφ密度与总生存率呈负相关（均P < 0.01）。多因素分析显示ST段浸润CD 204 + Mφ密度是影响总生存率的独立预后因素（HR，1.981; P = 0.022）。ST段浸润的CD 204 + Mφs密度与肿瘤大小（P = 0.001）、肿瘤分期（P < 0.0001）、淋巴结转移（P <0.0001）和组织学分级（P < 0.0001）呈正相关。我们的研究结果表明，CD 204 + Mφs可能发挥有害的促肿瘤作用，并代表了人类膀胱癌中的主要Mφ表型。
Macrophages (Mφs) are a major cell type that can infiltrate solid tumors and exhibit distinct phenotypes in different tumor microenvironments. This study attempted to investigate the prognostic values of various tumor-infiltrating Mφ phenotypes in patients with urothelial cell carcinoma of the bladder (UCB), with a focus on Mφ tissue microlocalization. Mφs were assessed by immunohistochemistry in tissues from 302 UCB patients using CD68 as a pan-Mφ marker, and CD204 and CD169 as robust pro- and anti-tumoral Mφ phenotype markers, respectively. Our data showed that these Mφ phenotypes were predominately distributed in stromal (ST) rather than in intratumoral (INT) regions (all P < 0.0001). Surprisingly, CD204 and CD169 can be co-expressed by the same CD68+ Mφs. Kaplan-Meier analysis revealed that all INT- and ST-infiltrating CD204+ or CD169+ Mφ densities were inversely associated with overall survival (all P < 0.01). By multivariate analysis, ST-infiltrating CD204+ Mφ density emerged as an independent prognostic factor for overall survival (HR, 1.981; P = 0.022). Moreover, the density of ST-infiltrating CD204+ Mφs was positively associated with the tumor size (P = 0.001), tumor stage (P < 0.0001), nodal metastasis (P < 0.0001), and histological grade (P < 0.0001). Our findings suggest that CD204+ Mφs might play detrimental protumoral roles and represent the predominant Mφ phenotype in human bladder cancer.