Department of Urology, Tokyo Medical and Dental Graduate University, Tokyo, Japan.
Department of Urology, Tokyo Medical and Dental Graduate University, Tokyo, Japan.
Clin Genitourin Cancer. 2018 Dec;16(6):e1151-e1158. doi: 10.1016/j.clgc.2018.07.027. Epub 2018 Aug 11.
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.
Immunohistochemical measurement of CD4, CD8, CD163 (M2 macrophages), and Foxp3 (Regulatory T [Treg] 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.
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.
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-反应蛋白（CRP）是一种代表性的炎症标志物，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，其详细机制尚不清楚。本研究表明，较高的 CRP 水平与肿瘤免疫微环境相关，从而导致预后较差。这些发现有助于阐明全身炎症反应与预后之间的潜在机制。本研究的目的是探讨肾细胞癌（RCC）患者肿瘤免疫微环境与 CRP 之间的关系，以探讨 CRP 水平与预后之间的潜在机制。
对在我院接受根治性或部分肾切除术的 111 例透明细胞 RCC 患者进行 CD4、CD8、CD163（M2 巨噬细胞）和 Foxp3（调节性 T [Treg] 细胞）的免疫组织化学测量。分析免疫组织化学状态与术前血清 CRP 水平和癌症特异性生存（CSS）之间的关系。
33 例（30%）患者 CRP 水平较高（≥5.0mg/L），这些患者的 CSS 率明显低于其余患者（P<0.001）。CD8+、Foxp3+或 CD163+细胞浸润较强的患者 CRP 水平明显较高（P=0.041、P=0.001 和 P=0.035），CSS 明显较浸润较弱的患者差（P=0.040、P=0.026 和 P<0.001）。多变量分析显示，CD163+细胞浸润较强（P=0.001）以及病理 T3（P=0.036）、淋巴结受累（P=0.007）、远处转移（P<0.001）和 Fuhrman 核分级 4（P=0.003）是 CSS 的独立预后因素。
在肿瘤微环境中浸润已知的免疫抑制细胞 Tregs 和 M2 巨噬细胞与透明细胞 RCC 患者较高的 CRP 和较差的预后相关。CRP 可能反映了一种免疫抑制的微环境。
