中文摘要
TIL(肿瘤浸润淋巴细胞)在透明细胞肾细胞癌(ccRCC)的发病和进展中发挥关键作用,这一点已得到充分证实。然而,肿瘤免疫微环境中TIL与肿瘤细胞相互作用的机制仍不清楚。本研究采用免疫组织化学评估补体反应基因32(RGC-32)的表达,分析其与患者特征及生存结局的关联,并评估肿瘤细胞巢中的TIL及其亚群(CD3⁺、CD4⁺、CD8⁺和PD-1⁺)。RGC-32表达水平与ISUP分级和Ki-67表达呈正相关,并且是ccRCC患者不良预后的独立因素。RGC-32表达与TIL和CD3⁺ T细胞浸润呈负相关,但与PD-1⁺细胞浸润呈正相关。体外研究显示,免疫细胞活化后,肾癌细胞中的RGC-32表达下调。进一步研究发现,活化免疫细胞分泌的TNF-α和IL-1可抑制肾癌细胞中的RGC-32表达。综合而言,这些数据提示,RGC-32可能是与肾癌肿瘤免疫微环境相关的新型预后标志物和可成药靶点。
展开英文摘要原文
It has been well established that tumor-infiltrating lymphocytes (TILs) play a critical role in the pathogenesis and progression of clear cell renal cell carcinoma (ccRCC).
However, the mechanism on the interactions between TILs and tumor cells in the tumor-immune microenvironment remains unclear. In the present study, the expression of Response Gene to Complement 32 (RGC-32) was evaluated using immunohistochemistry.
We analyzed the associations of RGC-32 expression with patient characteristics and survival.
We also assessed TILs and their subsets (CD3 + , CD4 + , CD8 + and PD-1 + ) in the tumor nest. The level of RGC-32 expression was positively correlated with ISUP grade and Ki67 expression and was an independent poor prognosis factor of patients with ccRCC. RGC-32 expression was negatively correlated with the infiltration of TIL and CD3 + T cells, but positively correlated with infiltration of PD-1 + cells. In vitro studies showed that RGC-32 expression in renal cancer cells was downregulated by activated immune cells.
Further investigation revealed that RGC-32 expression in renal cancer cells was inhibited by TNF- and IL-1 secreted by activated immune cells. Collectively, these data indicate that RGC-32 could be a novel prognostic and druggable target related to the tumor-immune microenvironment in renal cancer.
论文信息
- 作者
- Li L、Bu X、Wang S、Liu Y、Chen C、Zhang W、Zhao P
- 第一作者单位
- School of Basic Medicine, Shandong Second Medical University, Weifang, China.China
- 通讯作者单位
- Biotherapy Center, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, China. Electronic address: zp8102@126.com.China
- 期刊
- Translational oncology2025 Feb