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Cortisol facilitates the immune escape of human acute myeloid leukemia cells by inducing latrophilin 1 expression

Cellular & Molecular Immunology volume 15, pages 994–997 (2018)Cite this article

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The progression of acute myeloid leukemia (AML)—the most severe blood/bone marrow cancer—is determined by the ability of malignant cells to escape host immune surveillance. However, the systemic regulatory mechanisms underlying this phenomenon remain largely unknown. In this study, we discovered a fundamental systemic biochemical strategy that allows AML cells to employ physiological systems within the body to survive and escape immune attack. We found that AML cells use a crucial human adrenal cortex hormone (cortisol) to induce the expression of neuronal receptor latrophilin 1 (LPHN1), which facilitates exocytosis. This receptor interacts with the blood plasma protein fibronectin leucine rich transmembrane protein 3 (FLRT3) to cause secretion of the immune suppressor galectin-9, which impairs the anticancer activities of cytotoxic lymphoid cells.

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Acknowledgements

This work was supported by a Daphne Jackson Trust postdoctoral fellowship (to I. M. Y.) and the University of Kent Faculty of Sciences Research Fund (to V. S.). We thank Diamond Light Source for access to B23 beamline (SM12578).

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Authors and Affiliations

  1. Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, UK

    Svetlana S. Sakhnevych, Inna M. Yasinska, Alison M. Bratt, Ouafa Benlaouer, Isabel Gonçalves Silva, Bernhard F. Gibbs, Yuri A. Ushkaryov & Vadim V. Sumbayev

  2. Beamline B23, Diamond Light Source, Didcot, UK

    Rohanah Hussain & Giuliano Siligardi

  3. Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Walter Fiedler & Jasmin Wellbrock

  4. Department of Medicine, Dermatology and Allergology, University of Oldenburg, Oldenburg, Germany

    Bernhard F. Gibbs

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  1. Svetlana S. Sakhnevych
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Correspondence to Vadim V. Sumbayev.

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Sakhnevych, S.S., Yasinska, I.M., Bratt, A.M. et al. Cortisol facilitates the immune escape of human acute myeloid leukemia cells by inducing latrophilin 1 expression. Cell Mol Immunol 15, 994–997 (2018). https://doi.org/10.1038/s41423-018-0053-8

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