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Proteasome-guided haem signalling axis contributes to T cell exhaustion

read original get T Cell Exhaustion Research Kit → more articles
Why This Matters

This research highlights the intricate mechanisms behind T cell exhaustion, particularly the role of proteasome-guided haem signaling and mitochondrial dynamics. Understanding these pathways is crucial for developing more effective immunotherapies for cancer and chronic infections, ultimately improving patient outcomes. Advances in this area could lead to enhanced T cell resilience and sustained immune responses in clinical settings.

Key Takeaways

Yu, Y. R. et al. Disturbed mitochondrial dynamics in CD8+ TILs reinforce T cell exhaustion. Nat. Immunol. 21, 1540–1551 (2020).

Scharping, N. E. et al. Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion. Nat. Immunol. 22, 205–215 (2021).

Vardhana, S. A. et al. Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen. Nat. Immunol. 21, 1022–1033 (2020).

Franco, F., Jaccard, A., Romero, P., Yu, Y. R. & Ho, P. C. Metabolic and epigenetic regulation of T-cell exhaustion. Nat. Metab. 2, 1001–1012 (2020).

McLane, L. M., Abdel-Hakeem, M. S. & Wherry, E. J. CD8 T cell exhaustion during chronic viral infection and cancer. Annu. Rev. Immunol. 37, 457–495 (2019).

Blank, C. U. et al. Defining ‘T cell exhaustion’. Nat. Rev. Immunol. 19, 665–674 (2019).

Zhou, P. et al. Single-cell CRISPR screens in vivo map T cell fate regulomes in cancer. Nature 624, 154–163 (2023).

Beltra, J. C. et al. Developmental relationships of four exhausted CD8+ T cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms. Immunity 52, 825–841 (2020).

Utzschneider, D. T. et al. Early precursor T cells establish and propagate T cell exhaustion in chronic infection. Nat. Immunol. 21, 1256–1266 (2020).

Daniel, B. et al. Divergent clonal differentiation trajectories of T cell exhaustion. Nat. Immunol. 23, 1614–1627 (2022).

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