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Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion

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Abstract

Recent clinical data support ideas of Programmed death receptor-ligand 1 (PD-L1; also called B7-H1, CD274) playing an important role in immune evasion of tumor cells. Expression of PD-L1 on tumors strongly correlates with the survival of cancer patients. PD-L1 on tumors interacts with the co-inhibitory molecule Programmed death receptor-1 (PD-1, CD279) on T cells mediating decreased TCR-mediated proliferation and cytokine production. In animal tumor models, blockade of PD-L1/PD-1 interactions resulted in an improved tumor control. In addition, exhausted T cells during chronic viral infections could be revived by PD-L1 blockade. Thus, targeting PD-L1/PD-1 interactions might improve the efficacy of adoptive cell therapies (ACT) of chronic infections as well as cancers. Obstacles for a general blockade of PD-L1 might be its role in mediating peripheral tolerance. This review discusses the currently available data concerning the role of PD-L1 in tumor immune evasion and envisions possibilities for implementation into ACT for cancer patients.

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Acknowledgment

Dr. Christian Blank is supported by the Deutsche Krebshilfe e.V. Grant No. 10-2204-Bl 1.

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  1. Department of Hematology and Oncology, University of Regensburg, Franz-Josef Strauss Allee 11, 93042, Regensburg, Germany

    Christian Blank & Andreas Mackensen

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Correspondence to Christian Blank.

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This article is a symposium paper from the conference “Cancer Immunotherapy 2006 Meets Strategies for Immune Therapy,-held in Mainz, Germany, on 4- May 2006.

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Blank, C., Mackensen, A. Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother 56, 739–745 (2007). https://doi.org/10.1007/s00262-006-0272-1

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