Journal article
MYB orchestrates T cell exhaustion and response to checkpoint inhibition
C Tsui, L Kretschmer, S Rapelius, SS Gabriel, D Chisanga, K Knöpper, DT Utzschneider, S Nüssing, Y Liao, T Mason, SV Torres, SA Wilcox, K Kanev, S Jarosch, J Leube, SL Nutt, D Zehn, IA Parish, W Kastenmüller, W Shi Show all
Nature | NATURE PORTFOLIO | Published : 2022
Abstract
CD8+ T cells that respond to chronic viral infections or cancer are characterized by the expression of inhibitory receptors such as programmed cell death protein 1 (PD-1) and by the impaired production of cytokines. This state of restrained functionality—which is referred to as T cell exhaustion1,2—is maintained by precursors of exhausted T (TPEX) cells that express the transcription factor T cell factor 1 (TCF1), self-renew and give rise to TCF1− exhausted effector T cells3–6. Here we show that the long-term proliferative potential, multipotency and repopulation capacity of exhausted T cells during chronic infection are selectively preserved in a small population of transcriptionally distin..
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Awarded by National Institutes of Health
Funding Acknowledgements
We acknowledge I. Andra and M. Schiemann for cell sorting, and R. Gloury and I. Hensel for technical help. This work was supported by the National Health and Medical Research Council of Australia (NHMRC) Research Fellowship (to A.K.) and Ideas Grants (APP2004333 to A.K. and C.T.; APP2001719 to I.A.P.); the European Research Council (starting grant 949719 SCIMAP to V.R.B.); the Else Kroner-Fresenius-Stiftung (EKFS 2019_A91 to V.R.B.); the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation; SFB-TRR 338/1 2021-452881907, SFB 1054-210592381 to V.R.B.); and the Deutsche Krebshilfe (DKH 70113918 to V.R.B). A.K. is a Senior Research Fellow of the NHMRC; D.T.U. is a Special Fellow of The Leukemia & Lymphoma Society and is supported by an NHMRC fellowship (1194779). We acknowledge the Melbourne Cytometry Platform for provision of flow cytometry services and the NIH Tetramer Facility for providing tetramers.