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Updated: May 28, 2026

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
Targeting UBE2F induces a resilience program enhancing CD8 T cell immunity
Xiaonan Ma1,2,3,4, Henan Guo1,2,3, Yuting Jia2
1State Key Laboratory of Molecular Oncology, Institute for Immunology, Beijing Key Laboratory for Mechanisms and Drug Development of Allergic Diseases, School of Basic Medical Sciences, Tsinghua Medicine, Tsinghua University , Beijing, China.
None:
Memory CD8 T cells (TMEM) and exhausted CD8 T cells (TEX) are essential for host defense against infection and cancer, yet their therapeutic potential is often limited by insufficient persistence and sustained functional capacity. Strategies to enhance the longevity of both populations remain scarce. Here, we demonstrate that ablation of UBE2F, a neddylation E2 enzyme, induces a resilience program in CD8 T cells that operates across both TMEM and TEX compartments, resulting in improved viral and tumor control. This resilience state is characterized by enhanced self-renewal and survival without perturbing the conventional CD8 T cell differentiation trajectories. Mechanistically, UBE2F deficiency inhibited neddylation of CUL5, leading to accumulation of JUNB and upregulation of IL-2Rβ. The increased IL-2Rβ expression hypersensitizes CD8 T cells to physiological IL-15, thereby conferring the resilience features. Together, these findings identify the UBE2F-CUL5-JUNB-IL-2Rβ axis as a conserved posttranslational mechanism regulating CD8 T cell longevity across memory and exhausted states, providing a novel strategy for enhancing antiviral and antitumor immunity.
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