转移性肾细胞癌（mRCC）目前仍然无法治愈，尽管当前的检查点阻滞驱动的总体反应率有限。CD8+记忆T细胞能够发挥迅速和有效的反应。尚未探索泛素连接酶RAD6-KCMF1-UBR4介导的自噬在患有肾细胞癌（RCC）的CD8+记忆T细胞中的调节作用。因此，采用流式细胞术研究了记忆T细胞及其亚型在周围血单个核细胞（PBMCs）中的激活和调节表型。在RCC患者的记忆T细胞中，以细胞和分子水平测定了泛素连接酶和自噬的表达。使用JC.1染色和Annexin/PI测定来评估记忆T细胞去极化和凋亡率。结果表明，Ub-E2-E3复合物的破坏和记忆T细胞中受损的自噬降低了它们对抗肿瘤细胞的生存和作战能力。通过靶向E3泛素连接酶或自噬途径抑制记忆T细胞凋亡可以作为潜在的治疗策略，以改善RCC中记忆T细胞的长期生存。版权所有©2023 Elsevier B.V.发表。

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.Copyright © 2023. Published by Elsevier B.V.