Unlocking a New Frontier in Cancer Immunotherapy: UFL1 Ablation Unleashes the Power of T Cells
Dr. Yu-Ru Lee from Academia Sinica, with Dr. Hsin-Yi Chen as the co-first author, published a breakthrough study in Molecular Cell on February 19, 2024. In this study, Dr. Yu-Ru Lee’s group has unveiled a novel mechanism that holds the key to enhancing anti-tumor immunity. The study, titled "UFL1 Ablation in T Cells Suppresses PD-1 UFMylation to Enhance Anti-tumor Immunity," explores the intricate world of UFMylation, an emerging post-translational modification, and its profound impact on T cell function.
The researchers focused on UFL1, a UFMylation E3 ligase, and conducted a groundbreaking experiment involving conditional knockout (cKO) of Ufl1 in T cells. The results were nothing short of revolutionary, showcasing enhanced tumor control in mice with Ufl1 cKO.
Moreover, Single-cell RNA sequencing brought deeper insights, revealing a substantial increase in tumor-infiltrating cytotoxic CD8+ T cells in Ufl1 cKO mice. The study also sheds light on the role of UFL1 in promoting PD-1 UFMylation, a crucial process that counters PD-1 ubiquitination and safeguards it from degradation.
Not stopping there, the researchers uncovered that AMPK phosphorylation of UFL1 at Thr536 disrupts PD-1 UFMylation, leading to its degradation. This revelation is a game-changer, suggesting a potential pathway for targeted cancer therapies.
Most notably, UFL1 ablation in T cells was found to reduce PD-1 UFMylation, destabilizing PD-1 and significantly boosting CD8+ T cell activation. This finding has far-reaching implications, suggesting a promising strategy for improving responses to anti-CTLA-4 immunotherapy.
In the quest to unravel the mysteries of UFMylation, this study not only deepens our understanding of T cell dynamics but also opens doors to innovative approaches in cancer immunotherapy. The implications of these findings are vast, offering hope for a new era in the fight against cancer.
This research, a joint effort with the team from Dr. Shih-Yu Chen’s group in IBMS, Academia Sinica and the team from Dr. Jinfang Zhang’s group in Wuhan University marks a significant step forward in the quest for effective cancer treatments. The exploration of novel PD-1 UFMylation in T cells, particularly its influence on anti-tumor immunity, offers promising prospects for future research and therapeutic interventions. For more information, please contact Dr. Yu-Ru Lee at Institution of Biomedical Sciences, Academia Sinica.
Contact:
Dr. Yu-Ru Lee, Assistant Research Fellow at Institute of Biomedical Sciences, Academia Sincia
(Tel) +886-2-26523931, yrlee@ibms.sinica.edu.tw