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PD-L1-specific T cells

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Abstract

Recently, there has been an increased focus on the immune checkpoint protein PD-1 and its ligand PD-L1 due to the discovery that blocking the PD-1/PD-L1 pathway with monoclonal antibodies elicits striking clinical results in many different malignancies. We have described naturally occurring PD-L1-specific T cells that recognize both PD-L1-expressing immune cells and malignant cells. Thus, PD-L1-specific T cells have the ability to modulate adaptive immune reactions by reacting to regulatory cells. Thus, utilization of PD-L1-derived T cell epitopes may represent an attractive vaccination strategy for targeting the tumor microenvironment and for boosting the clinical effects of additional anticancer immunotherapy. This review summarizes present information about PD-L1 as a T cell antigen, depicts the initial findings about the function of PD-L1-specific T cells in the adjustment of immune responses, and discusses future opportunities.

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Abbreviations

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

FDA:

Food and Drug Administration

iNOS:

Inducible nitric oxide synthases

IRF-1:

IFN regulatory factor-1

MM:

Metastatic melanoma

TADC:

Tumor-associated dendritic cells

TAP:

Transporter associated with antigen processing

TDO:

Tryptophan 2,3-dioxygenase

Tregs:

Regulatory T cells

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Acknowledgments

This work was supported by the Danish Cancer Society, the Danish Council for Independent Research, Lundbeck Foundation, Toyota Foundation, and Herlev Hospital. The funders did not have a role in the writing of the article or the decision to submit the article for publication

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Authors and Affiliations

  1. Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Herlev Ringvej 75, 2730, Herlev, Denmark

    Shamaila Munir Ahmad, Troels Holz Borch, Morten Hansen & Mads Hald Andersen

  2. Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark

    Mads Hald Andersen

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  1. Shamaila Munir Ahmad
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  2. Troels Holz Borch
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  3. Morten Hansen
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  4. Mads Hald Andersen
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Correspondence to Mads Hald Andersen.

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Conflict of interest

Mads Hald Andersen is an author of three filed patent applications based on the use of PD-L1 vaccination. The rights of the patent applications have been transferred to Copenhagen University Hospital, Herlev/The Capital Region of Denmark, according to the Danish Law of Public Inventions at Public Research Institutions. All other authors declare no conflict of interest.

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Ahmad, S.M., Borch, T.H., Hansen, M. et al. PD-L1-specific T cells. Cancer Immunol Immunother 65, 797–804 (2016). https://doi.org/10.1007/s00262-015-1783-4

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