| Title: |
Antigen and checkpoint receptor engagement recalibrates T cell receptor signal strength |
| Authors: |
Elliot, Thomas A.E.; Jennings, Emma K.; Lecky, David A.J.; Natash, Natasha; Flores-Langarica, Adriana; Copland, Alastair; Maslowski, Kendle M.; Wraith, David C.; Bending, David |
| Publisher Information: |
Cell Press |
| Publication Year: |
2021 |
| Collection: |
University of Glasgow: Enlighten - Publications |
| Description: |
How T cell receptor (TCR) signal strength modulates T cell function and to what extent this is modified by immunecheckpoint blockade (ICB) are key questions in immunology. Using Nr4a3-Tocky mice, we characterized early quantitative and qualitative changes that occur in CD4+ T cells in relation to TCR signaling strength. We captured how dose- and time-dependent programming of distinct co-inhibitory receptors rapidly recalibrates T cell activation thresholds and visualized the immediate effects of ICB on T cell re-activation. Our findings reveal that anti-PD1 immunotherapy leads to an increased TCR signal strength. We defined a strong TCR signal metric of five genes upregulated by anti-PD1 in T cells (TCR.strong), which was superior to a canonical T cell activation gene signature in stratifying melanoma patient outcomes to anti-PD1 therapy. Our study therefore reveals how analysis of TCR signal strength—and its manipulation— can provide powerful metrics for monitoring outcomes to immunotherapy. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://eprints.gla.ac.uk/379063/1/379063.pdf; Elliot, Thomas A.E., Jennings, Emma K., Lecky, David A.J., Natash, Natasha, Flores-Langarica, Adriana, Copland, Alastair, Maslowski, Kendle M. ORCID logoorcid:0000-0003-1995-5424 , Wraith, David C. and Bending, David (2021) Antigen and checkpoint receptor engagement recalibrates T cell receptor signal strength. Immunity , 54(11), 2481-2496.e6. (doi:10.1016/j.immuni.2021.08.020 ) (PMID:34534438) (PMCID:PMC8585507) |
| DOI: |
10.1016/j.immuni.2021.08.020 |
| Availability: |
https://eprints.gla.ac.uk/379063/; https://eprints.gla.ac.uk/379063/1/379063.pdf; https://doi.org/10.1016/j.immuni.2021.08.020 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.49D38CD2 |
| Database: |
BASE |