Higher Serum C-reactive Protein Level Represents the Immunosuppressive Tumor Microenvironment in Patients With Clear Cell Renal Cell Carcinoma
Higher Serum C-reactive Protein Level Represents the Immunosuppressive Tumor Microenvironment in Patients With Clear Cell Renal Cell Carcinoma
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DOI：
10.1016/j.clgc.2018.07.027
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发表时间：
2018-12-01
影响因子：
3.2
通讯作者：
Fujii, Yasuhisa
中科院分区：
文献类型：
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作者：
Nakayama, Takayuki;Saito, Kazutaka;Fujii, Yasuhisa
本研究旨在评估111例肾细胞癌患者血清C反应蛋白水平与肿瘤免疫微环境之间的关系，这些免疫微环境来自于CD 4、CD 8、CD 163（M2巨噬细胞）和Foxp 3（调节性T细胞）的免疫组织化学染色。结果表明，血清C反应蛋白水平反映了肾细胞癌患者免疫抑制的肿瘤微环境。引言：C反应蛋白（CRP）是一种典型的炎症标志物，可作为肾细胞癌的生物标志物，因为CRP是一个重要的预后因素。然而，其详细机制仍然未知。这项研究表明，较高的CRP水平与肿瘤免疫微环境相关，这导致预后较差。这些发现有助于阐明全身炎症反应的存在与预后之间的潜在机制。本研究旨在探讨肾细胞癌（RCC）患者肿瘤免疫微环境与CRP的关系，探讨CRP水平与预后的可能机制。患者和方法：在我们的机构中，对接受根治性或部分肾切除术的透明细胞RCC患者（n = 111）进行了CD 4、CD 8、CD 163（M2巨噬细胞）和Foxp 3（调节性T [Treg 1细胞）的免疫组织化学测量。分析免疫组化状态与术前血清CRP水平和癌症特异性生存期（CSS）之间的关系。结果如下：33例患者（30%）CRP水平较高（>= 5.0 mg/L），这些患者的CSS率明显低于其余患者（P <0.001）。在CD 8+、Foxp 3+或CD 163+细胞强浸润的患者中，CRP水平显著高于弱浸润患者（分别为P = 0.041、P = 0.001和P = 0.035），CSS显著差于弱浸润患者（分别为P = 0.040、P = 0.026和P <0.001）。在多变量分析中，强CD 163细胞浸润（P =.001）以及病理T3（P =.036）、淋巴结受累（P =.007）、远处转移（P < .001）和Fuhrman核分级4（P =.003）是CSS的独立预后因素。结论：在透明细胞肾细胞癌患者中，肿瘤微环境中的免疫抑制细胞（称为TCR 4和M2巨噬细胞）的浸润与较高的CRP和不良预后相关。CRP可以反映免疫抑制的微环境。(C)2018爱思唯尔公司All rights reserved.
This study was designed to assess the association between serum C-reactive protein level and tumor immune microenvironment derived from immunohistochemical staining for CD4, CD8, CD163 (M2 macrophages), and Foxp3 (regulatory T cells) in 111 patients with dear-cell renal cell carcinoma. The results indicated serum Creactive protein level reflects the immunosuppressive tumor microenvironment in patients with dear-cell renal cell carcinoma.Introduction: C-reactive protein (CRP), a representative inflammatory marker, could serve as a biomarker in renal cell carcinoma because CRP is an important prognostic factor. However, its detailed mechanism remains unknown. This study showed that higher CRP levels correlated with the tumor immune microenvironment, which leads to a worse prognosis. These findings can help to clarify the underlying mechanisms between the presence of systemic inflammatory reaction and prognosis. The aim of this study is to investigate the association between tumor immune microenvironment and CRP in patients with renal cell carcinoma (RCC) to explore the underlying mechanisms between CRP level and prognosis. Patients and Methods: Immunohistochemical measurement of CD4, CD8, CD163 (M2 macrophages), and Foxp3 (Regulatory T [Tregl cells) was performed in patients with clear-cell RCC (n = 111) treated with radical or partial nephrectomy at our institution. The association between immunohistochemical status and preoperative serum CRP level and cancer-specific survival (CSS) was analyzed. Results: Thirty-three patients (30%) had a high CRP level (>= 5.0 mg/L), and the CSS rate was significantly worse among these patients than among the remaining patients (P < .001). In patients with strong infiltration of CD8+ , Foxp3+ , or CD163+ cells, CRP levels were significantly higher (P =.041, P =.001, and P =.035, respectively), and CSS was significantly worse compared with patients with weak infiltration (P =.040, P =.026, and P < .001, respectively). In multivariate analysis, strong CD163 cells infiltration (P =.001) as well as pathologic T3 (P =036), lymph-node involvement (P =.007), distant metastasis (P < .001), and Fuhrman nuclear grade 4 (P =.003) were independent prognostic factors for CSS. Conclusions: Infiltration of the immunosuppressive cells known as Tregs and M2 macrophages in the tumor microenvironment is associated with higher CRP and poor prognosis in patients with clear-cell RCC. CRP could reflect an immunosuppressive microenvironment. (C) 2018 Elsevier Inc. All rights reserved.