Selvi Ismail, Demirci Umut, Bozdogan Nazan, Basar Halil
Department of Urology, Karabük University Training and Research Hospital, 78200, Karabük, Turkey.
Department of Medical Oncology, Health Science University Dr, Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey.
Int Urol Nephrol. 2020 Jan;52(1):21-34. doi: 10.1007/s11255-019-02285-0. Epub 2019 Sep 20.
This study aimed to evaluate the density of CD8 and CD3 tumor-infiltrating lymphocytes (TILs) and determine whether the immunoscore has any prognostic effect on the oncological outcomes in patients with clear cell renal cell carcinoma (RCC).
A total of 129 patients diagnosed with clear cell RCC following radical or partial nephrectomy between 2009 and 2014 were retrospectively analyzed. Both tumor core (CT) and the invasive margin of nephrectomy specimens were assessed. The specimens were immunostained for anti-CD8 and anti-CD3 TILs. The patients were divided into three groups (favorable, intermediate, and poor risk) according to immunoscore levels.
In the multivariate analysis, a favorable immunoscore (I3-4) was associated with prolonged disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) (HR 2.652, 2.848, and 2.933, respectively; all p < 0.001). The lower Fuhrman grade and pathological tumor-node-metastasis (TNM) stage had better DFS, PFS, and OS, whereas prolonged PFS was associated with a higher density of CD8 CT (HR 1.602, 95% CI 0.934-3.470; p = 0.014). The shorter DFS, PFS, and OS were observed in the group with poor immunoscore (I0-1) at the early TNM stage of RCC (p < 0.001). In the metastatic subgroup analysis, the immunoscore showed better estimation than the International Metastatic RCC Database Consortium model and the Memorial Sloan-Kettering Cancer Center risk model for progression and OS (p < 0.001).
The additional contributions of immunoscore to TNM stage, Fuhrman grade, and the WHO/ISUP 2016 grade for estimating oncological outcomes were found in ROC analysis. According to our preliminary results, immunoscore can be a promising prediction tool in clear cell RCC for postoperative oncological outcomes following nephrectomy.
本研究旨在评估CD8和CD3肿瘤浸润淋巴细胞（TILs）的密度，并确定免疫评分对透明细胞肾细胞癌（RCC）患者肿瘤学结局是否具有预后作用。
回顾性分析了2009年至2014年间129例接受根治性或部分肾切除术后诊断为透明细胞RCC的患者。对肾切除标本的肿瘤核心（CT）和浸润边缘进行评估。标本进行抗CD8和抗CD3 TILs免疫染色。根据免疫评分水平将患者分为三组（低危、中危和高危）。
在多因素分析中，良好的免疫评分（I3 - 4）与无病生存期（DFS）、无进展生存期（PFS）和总生存期（OS）延长相关（HR分别为2.652、2.848和2.933；均p < 0.001）。较低的Fuhrman分级和病理肿瘤-淋巴结-转移（TNM）分期具有更好的DFS、PFS和OS，而PFS延长与CD8 CT的较高密度相关（HR 1.602，95%CI 0.934 - 3.470；p = 0.014）。在RCC早期TNM分期中，免疫评分差（I0 - 1）组观察到较短的DFS、PFS和OS（p < 0.001）。在转移亚组分析中，免疫评分在预测进展和OS方面比国际转移性RCC数据库联盟模型和纪念斯隆凯特琳癌症中心风险模型表现更好（p < 0.001）。
在ROC分析中发现免疫评分对TNM分期、Fuhrman分级和WHO/ISUP 2016分级在评估肿瘤学结局方面有额外贡献。根据我们的初步结果，免疫评分可能是透明细胞RCC肾切除术后肿瘤学结局的一种有前景的预测工具。
