Li, Chaofan and Zhu, Bibo and Son, Young Min and Wang, Zheng and Jiang, Li and Xiang, Min and Ye, Zhenqing and Beckermann, Kathryn E. and Wu, Yue and Jenkins, James W. and Siska, Peter J. and Vincent, Benjamin G. and Prakash, Y. S. and Peikert, Tobias and Edelson, Brian T. and Taneja, Reshma and Kaplan, Mark H. and Rathmell, Jeffrey C. and Dong, Haidong and Hitosugi, Taro and Sun, Jie (2019) The Transcription Factor Bhlhe40 Programs Mitochondria! Regulation of Resident CD8(+) T Cell Fitness and Functionality. IMMUNITY, 51 (3). 491-+. ISSN 1074-7613, 1097-4180
Full text not available from this repository. (Request a copy)Abstract
Tissue-resident memory CD8(+) T (Trm) cells share core residency gene programs with tumor-infiltrating lymphocytes (TILs). However, the transcriptional, metabolic, and epigenetic regulation of Trm cell and TIL development and function is largely undefined. Here, we found that the transcription factor Bhlhe40 was specifically required for Trm cell and TIL development and polyfunctionality. Local PD-1 signaling inhibited TIL Bhlhe40 expression, and Bhlhe40 was critical for TIL reinvigoration following anti-PD-L1 blockade. Mechanistically, Bhlhe40 sustained Trm cell and TIL mitochondria! fitness and a functional epigenetic state. Building on these findings, we identified an epigenetic and metabolic regimen that promoted Trm cell and TIL gene signatures associated with tissue residency and polyfunctionality. This regimen empowered the anti-tumor activity of CD8(+) T cells and possessed therapeutic potential even at an advanced tumor stage in mouse models. Our results provide mechanistic insights into the local regulation of Trm cell and TIL function.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TISSUE-RESIDENT; TUMOR MICROENVIRONMENT; DENDRITIC CELLS; MEMORY; INFECTION; PD-L1; ACTIVATION; IMMUNITY; SUPPRESSION; DYSFUNCTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Mar 2020 12:25 |
| Last Modified: | 27 Mar 2020 12:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26238 |
Actions (login required)
 |
View Item |
