Sanders Christine, Hamad Almotasem Salah M, Ng Susanna, Hosni Racha, Ellinger Jörg, Klümper Niklas, Ritter Manuel, Stephan Carsten, Jung Klaus, Hölzel Michael, Kristiansen Glen, Hauser Stefan, Toma Marieta I
Institute of Pathology, University Hospital Bonn (UKB), 53127 Bonn, Germany.
Institute of Experimental Oncology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
Cancers (Basel). 2022 Mar 17;14(6):1541. doi: 10.3390/cancers14061541.
Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor with variable responses to immune checkpoint therapy. The significance of the immune cell infiltrate in distant metastases, their association with the immune infiltrate in the primary tumors and their impact on prognosis are poorly described. We hypothesized that specific subtypes of immune cells may be involved in the control of metastases and may have an impact on the prognosis of ccRCC. We analyzed the immune microenvironment in ccRCC primary tumors with distant metastases, paired distant metastases and non-metastasized ccRCC (n = 25 each group) by immunohistochemistry. Confirmatory analyses for CD8+ and CD103+ cells were performed in a large ccRCC cohort (n = 241) using a TCGA-KIRC data set (ITGAE/CD103). High immune cell infiltration in primary ccRCC tumors was significantly correlated with the development of distant tumor metastasis (p < 0.05). A high density of CD103+ cells in ccRCC was more frequent in poorly differentiated tumors (p < 0.001). ccRCCs showed high levels of ITGAE/CD103 compared with adjacent non-neoplastic tissue. A higher density of CD103+ cells and a higher ITGAE/CD103 expression were significantly correlated with poor overall survival in ccRCC (log rank p < 0.05). Our results show a major prognostic value of the immune pattern, in particular CD103+ cell infiltration in ccRCC, and highlight the importance of the tumor immune microenvironment.
透明细胞肾细胞癌(ccRCC)是一种具有高度免疫原性的肿瘤,对免疫检查点疗法有不同反应。远处转移中免疫细胞浸润的意义、它们与原发性肿瘤中免疫浸润的关联以及对预后的影响描述甚少。我们假设特定亚型的免疫细胞可能参与转移的控制,并可能对ccRCC的预后产生影响。我们通过免疫组织化学分析了伴有远处转移的ccRCC原发性肿瘤、配对的远处转移灶和未转移的ccRCC(每组n = 25)中的免疫微环境。使用TCGA-KIRC数据集(ITGAE/CD103)在一个大型ccRCC队列(n = 241)中对CD8 +和CD103 +细胞进行了验证性分析。原发性ccRCC肿瘤中高免疫细胞浸润与远处肿瘤转移的发生显著相关(p < 0.05)。在低分化肿瘤中,ccRCC中CD103 +细胞的高密度更为常见(p < 0.001)。与相邻的非肿瘤组织相比,ccRCC显示出高水平的ITGAE/CD103。CD103 +细胞的较高密度和较高的ITGAE/CD103表达与ccRCC的较差总生存期显著相关(对数秩检验p < 0.05)。我们的结果显示了免疫模式的主要预后价值,特别是ccRCC中CD103 +细胞浸润,并突出了肿瘤免疫微环境的重要性。