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The immunosuppressive ligands PD-L1 and CD200 are linked in AML T-cell immunosuppression: identification of a new immunotherapeutic synapse

Leukemia volume 29, pages 1952–1954 (2015)Cite this article

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Long-term remission in acute myeloid leukemia (AML) is generally not durable only being achieved in <50% of patients.1 Consequently there is a need to establish new treatments to prevent relapse. A promising approach is to augment the anti-tumor immune response in these patients; however, it is well established that overexpression of immunosuppressive molecules such as CD200 on the surface of AML cells directly suppresses the antitumor response.2, 3, 4 Nevertheless, blocking CD200:CD200R, only partially restores T-cell activity, suggesting that alternative immunosuppressive mechanisms need to be explored if the antitumor response in AML is to be optimally exploited.5

Recently, promising clinical outcomes using humanized antibodies targeting PD-1 have been reported for melanoma and even for non-small cell lung cancer.6 PD-1 suppresses immunological function via interaction with its cognate ligand PD-L1 (aka B7-H1, CD274) and previous work has indicated that PD-L1 may also suppress immunological function in AML.7, 8 Here we investigate whether the PD-1:PD-L1 axis cooperates with CD200 in mediating immunosuppression in AML patients.

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Acknowledgements

This work was funded by Leukaemia and Lymphoma Research UK and NISCHR, UK. RR is a CU/MRC UK funded student.

Author Contributions

SJC designed and performed the experiments, analyzed all data and cowrote the manuscript. MNG assisted with PD-L1 cloning and retroviral transduction. RR assisted with 7E7 T-cell expansion. SK and AKB provided resources and clinical insight. SM, AT and RLD contributed to experimental design and co-wrote the manuscript.

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Author notes

  1. S Man, A Tonks and R L Darley: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Science and the Environment, University of Worcester, Worcester, UK

    S J Coles

  2. Department of Haematology, Institute of Cancer and Genetics, School of Medicine, Cardiff University, Wales, UK

    S J Coles, M N Gilmour, R Reid, S Knapper, A K Burnett, S Man, A Tonks & R L Darley

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  1. S J Coles
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  2. M N Gilmour
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  3. R Reid
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  5. A K Burnett
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  6. S Man
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  7. A Tonks
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  8. R L Darley
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Correspondence to R L Darley.

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Coles, S., Gilmour, M., Reid, R. et al. The immunosuppressive ligands PD-L1 and CD200 are linked in AML T-cell immunosuppression: identification of a new immunotherapeutic synapse. Leukemia 29, 1952–1954 (2015). https://doi.org/10.1038/leu.2015.62

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