Reduced tumor-antigen density leads to PD-1/PD-L1 mediated impairment of partially exhausted CD8(+) T cells
Autor/innen
- A.D. Kaiser
- K. Schuster
- J. Gadiot
- L. Borkner
- H. Daebritz
- C. Schmitt
- R. Andreesen
- C. Blank
Journal
- European Journal of Immunology
Quellenangabe
- Eur J Immunol 42 (3): 662-671
Zusammenfassung
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.