Back to Search
Start Over
TOX-expressing terminally exhausted tumor-infiltrating CD8+ T cells are reinvigorated by co-blockade of PD-1 and TIGIT in bladder cancer.
- Source :
-
Cancer Letters . Feb2021, Vol. 499, p137-147. 11p. - Publication Year :
- 2021
-
Abstract
- Exhausted T cells in the tumor microenvironment are major targets of immunotherapies. However, the exhaustion status of CD8+ tumor-infiltrating lymphocytes (TILs) in bladder cancer has not been comprehensively evaluated. Herein, we examined distinct exhaustion status of CD8+ TILs based on the level of programmed cell death-1 (PD-1) and thymocyte selection-associated high mobility group box protein (TOX) expression in urothelial bladder cancer. We also evaluated the reinvigoration of exhausted CD8+ TILs upon ex vivo treatment with inhibitory checkpoint blockers. TOX-expressing PD-1highCD8+ TILs had the highest expression of immune checkpoint receptors (ICRs), the most terminally exhausted features, and the highest tumor antigen reactivity among PD-1+CD8+ TILs. Bladder cancer patients with a high percentage of PD-1highTOX+CD8+ TILs had more progressed T-cell exhaustion features and higher programmed death-ligand 1 expression in tumor tissues. TIGIT was the most frequent co-expressed ICR on PD-1+CD8+ TILs, and TIGIT blockade enhanced the PD-1 blockade-mediated cytokine production by CD8+ TILs from bladder cancer patients. Our findings provide an improved understanding of the heterogeneous exhaustion status of CD8+ TILs and additional immunotherapy strategies to improve outcomes of bladder cancer patients. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 499
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 147829843
- Full Text :
- https://doi.org/10.1016/j.canlet.2020.11.035