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Reduced tumor-antigen density leads to PD-1/PD-L1 mediated impairment of partially exhausted CD8(+) T cells

Item Type:Article
Title:Reduced tumor-antigen density leads to PD-1/PD-L1 mediated impairment of partially exhausted CD8(+) T cells
Creators Name:Kaiser, A.D. and Schuster, K. and Gadiot, J. and Borkner, L. and Daebritz, H. and Schmitt, C. and Andreesen, R. and Blank, C.
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.
Keywords:PD-1, PD-L1, T-Cells, Tumor Microenvironment, Animals, Mice
Source:European Journal of Immunology
ISSN:0014-2980
Publisher:Wiley (U.S.A.)
Volume:42
Number:3
Page Range:662-671
Date:March 2012
Official Publication:https://doi.org/10.1002/eji.201141931
PubMed:View item in PubMed

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