Tong Le, Kremer Veronika, Neo Shi Yong, Seitz Christina, Tobin Nicholas P, Seliger Barbara, Harmenberg Ulrika, Colón Eugenia, Scherman Plogell Ann-Helén, Liu Lisa L, Lundqvist Andreas
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Oncoimmunology. 2025 Dec;14(1):2481109. doi: 10.1080/2162402X.2025.2481109. Epub 2025 Mar 24.
Renal cell carcinoma (RCC) is recognized as an immunogenic tumor, yet tumor-infiltrating lymphocytes often exhibit diminished effector function. However, the mechanisms underlying reduced T and NK cell activity in RCC remain unclear. Here, we examined the immune contexture in RCC patients undergoing nephrectomy to identify immune-related biomarkers associated with disease progression. Immune cell phenotypes and secretion profiles were assessed using flow cytometry and Luminex multiplex analysis. Supervised multivariate analysis revealed several changes of which frequencies of T and NK cells expressing CCR5, CXCR3, and PD-1 were elevated within tumors compared with peripheral blood. In addition, higher levels of regulatory T cells, PD-1+, and CXCR3+ T and NK cells were observed in patients with relapse following nephrectomy. With regards to soluble factors, tumor-derived CXCL8 was associated with higher Fuhrman grade and increased frequency of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). These biomarkers demonstrate potential relevance in the progression of RCC and merit further investigation in prospective studies.
肾细胞癌（RCC）被认为是一种免疫原性肿瘤，然而肿瘤浸润淋巴细胞的效应功能往往会减弱。然而，RCC中T细胞和NK细胞活性降低的潜在机制仍不清楚。在这里，我们检查了接受肾切除术的RCC患者的免疫微环境，以确定与疾病进展相关的免疫相关生物标志物。使用流式细胞术和Luminex多重分析评估免疫细胞表型和分泌谱。多变量监督分析揭示了一些变化，与外周血相比，肿瘤内表达CCR5、CXCR3和PD-1的T细胞和NK细胞频率升高。此外，肾切除术后复发的患者中观察到调节性T细胞、PD-1+以及CXCR3+T细胞和NK细胞水平更高。关于可溶性因子，肿瘤来源的CXCL8与更高的富尔曼分级和多形核髓系来源抑制细胞（PMN-MDSC）频率增加相关。这些生物标志物表明在RCC进展中具有潜在相关性，值得在前瞻性研究中进一步研究。
