Disruption in networking of KCMF1 linked ubiquitin ligase impairs autophagy in CD8+ memory T cells of patients with renal cell carcinoma

Ashu Singh, Saumitra Dey Choudhury, Prabhjot Singh, Seema Kaushal, Alpana Sharma

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number216194
JournalCancer Letters
Volume564
DOIs
StatePublished - Jun 28 2023

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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