Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200040, China.
Aging (Albany NY). 2021 May 19;13(10):14304-14321. doi: 10.18632/aging.203045.
Renal cell carcinoma is characterized by high immunogenicity and infiltration of immune cells. CD45RO+CD8+ T cells are well known as a critical role in host defense of the immune environment. However, their role in clear cell renal carcinoma (ccRCC) remains unknown. To elucidate the clinical importance of CD45RO+CD8+ T cells in ccRCC as well as its underlying mechanism, we analyzed several types of peripheral immune cells from 274 patients with ccRCC who have received radical or partial nephrectomy and 350 healthy people. Flow cytomety assays showed there was no significant difference in the proportions of CD8+ T cells and its subtypes other than CD45RO+/CD45RA+CD8+ cells. Both gene and protein expression levels of CD45RO in ccRCC tissues were decreased. CD45RO+CD8+ T cells showed increased proliferative abilities but decreased apoptotic abilities through MAPK signaling activation in ccRCC. High expression level of CD45RO+CD8+ T cells inhibited ccRCC progression, including proliferation, invasion, as well as autophagy of ccRCC through many signaling pathways. Bioinformatics and immunohistochemical chip analysis measured gene and protein levels of CD45RO and other related proteins. The combination of UCHL1, HMGB3, and CD36 has diagnostic value in ccRCC and is able to predict prognosis. Collectively, CD45RO+CD8+ T cells play a critical role in ccRCC progression and may be regarded as clinical indicators.
肾细胞癌的特点是具有高度的免疫原性和免疫细胞浸润。CD45RO+CD8+T 细胞被认为在宿主免疫环境的防御中起着关键作用。然而,它们在透明细胞肾细胞癌(ccRCC)中的作用尚不清楚。为了阐明 CD45RO+CD8+T 细胞在 ccRCC 中的临床重要性及其潜在机制,我们分析了 274 例接受根治性或部分肾切除术的 ccRCC 患者和 350 例健康人的几种外周免疫细胞。流式细胞术检测显示,除 CD45RO+/CD45RA+CD8+细胞外,CD8+T 细胞及其亚型的比例无显著差异。ccRCC 组织中 CD45RO 的基因和蛋白表达水平均降低。CD45RO+CD8+T 细胞通过 MAPK 信号通路的激活,表现出增殖能力增强但凋亡能力降低。ccRCC 中 CD45RO+CD8+T 细胞的高表达水平通过多条信号通路抑制 ccRCC 的进展,包括增殖、侵袭和自噬。生物信息学和免疫组化芯片分析测量了 CD45RO 和其他相关蛋白的基因和蛋白水平。UCHL1、HMGB3 和 CD36 的组合在 ccRCC 中具有诊断价值,并能预测预后。总之,CD45RO+CD8+T 细胞在 ccRCC 的进展中起着关键作用,可作为临床指标。