Kaiser, Andrew D. and Schuster, Kerstin and Gadiot, Jules and Borkner, Lisa and Daebritz, Henry and Schmitt, Clemens and Andreesen, Reinhard and Blank, Christian (2012) Reduced tumor-antigen density leads to PD-1/PD-L1-mediated impairment of partially exhausted CD8+T cells. EUROPEAN JOURNAL OF IMMUNOLOGY, 42 (3). pp. 662-671. ISSN 0014-2980, 1521-4141
Full text not available from this repository. (Request a copy)Abstract
Clinical progression of cancer patients is often observed despite the presence of tumor-reactive T cells. Co-inhibitory ligands of the B7 superfamily have been postulated to play a part in this tumor-immune escape. One of these molecules, PD-L1 (B7-H1, CD274), is widely expressed on tumor cells and has been shown to mediate T-cell inhibition. However, attempts to correlate PD-L1 tumor expression with negative prognosis have been conflicting. To better understand when PD-1/PD-L1-mediated inhibition contributes to the functional impairment of tumor-specific CD8+ T cells, we varied the levels of antigen density and/or PD-L1 expression at the surface of tumor cells and exposed them to CD8+ T cells at different levels of functional exhaustion. We found that the gradual reduction of cognate antigen expression by PD-L1-expressing tumor cells increased the susceptibility of partially exhausted T cells to PD-1/PD-L1-mediated inhibition in vitro as well as in vivo. In conclusion, chronically stimulated CD8+ T cells become sensitive to PD-1/PD-L1-mediated functional inhibition upon low antigen detection; a setting which is likely involved during tumor-immune escape.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CD8(+) T-CELLS; SOLID TUMORS; B7-H1; PD-1; PATHWAY; LIGAND; PHASE; SUPPRESSION; LYMPHOCYTES; EXPRESSION; PD-1; PD-L1; T cells; Tumor microenvironment |
| 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: | 18 May 2020 10:57 |
| Last Modified: | 18 May 2020 10:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19085 |
Actions (login required)
 |
View Item |
