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This research investigates how the loss of UFL-1 influences CD8 T cell exhaustion independent of PD1 signaling.

PD1-independent CD8 T cell exhaustion driven by the loss of UFL-1 2260778

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Randomized trial explores UFL-1's role in CD8 T cell exhaustion, indicating new immunotherapy strategies.

This research investigates how the loss of UFL-1 influences CD8 T cell exhaustion independent of PD1 signaling.
Utilized LCMV acute and chronic infection models in control and UFL-1 knockout mice.
Analyzed CD8 T cell subsets and functional responses using flow cytometry and scRNA-seq.
Compared T cell exhaustion dynamics during acute and chronic antigen exposure.
UFL1-deficient CD8 T cells exhibit increased exhaustion during acute viral infections.
In chronic models, UFL1 deficiency exacerbates exhaustion, and PD1 blockade does not restore functionality in TEX cells.
Higher UFL1 expression in tumor-infiltrating CD8 T cells correlates with better survival in melanoma patients post-PD1 blockade.

Rathakrishnan et al. (2026) studied this question.

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