自噬
泛素连接酶
癌症研究
外周血单个核细胞
生物
泛素
流式细胞术
细胞毒性T细胞
记忆T细胞
CD8型
细胞生物学
免疫学
生物化学
细胞凋亡
免疫系统
体外
基因
作者
Ashu Singh,Saumitra Dey Choudhury,Prabhjot Singh,Seema Kaushal,Alpana Sharma
出处
期刊:Cancer Letters
[Elsevier]
日期:2023-04-20
卷期号:564: 216194-216194
被引量:6
标识
DOI:10.1016/j.canlet.2023.216194
摘要
Metastatic Renal Cell Carcinoma (mRCC) remains incurable, despite the current checkpoint-blockade-driven, limited overall response rate. The CD8+ memory T cells can mount a rapid and an effective response. The ubiquitin ligase RAD6-KCMF1-UBR4-mediated regulation of autophagy in CD8+ memory T cells in patients with renal cell carcinoma (RCC) remains unexplored. Consequently, flow cytometry was used to study memory T cells, and their subsets, including activation and regulatory phenotypes in peripheral blood mononuclear cells (PBMCs). Expression of the ubiquitin ligase and autophagy was measured both at the cellular and molecular levels in memory T cells of patients with RCC. JC.1 staining and Annexin/PI assays were used to evaluate the memory T cells depolarization and apoptosis rates. The results indicated that the disruption of Ub-E2-E3 complex and impaired autophagy in memory T cells diminished their ability to survive and combat against tumor cells. Inhibition of memory T cells apoptosis by targeting E3 ubiquitin ligase or autophagy pathways can be explored as a potential therapeutic strategy to improve the long-term survival of memory T cells in RCC.
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