Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

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

Dear Editor,

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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

References

  1. Estey, E. & Döhner, H. Acute myeloid leukaemia. Lancet 368, 1894–1907 (2006).

    Article  Google Scholar 

  2. Wyszynski, R. W., Gibbs, B. F., Varani, L., Iannotta, D. & Sumbayev, V. V. Interleukin-1 beta induces the expression and production of stem cell factor by epithelial cells: crucial involvement of the PI-3K/mTOR pathway and HIF-1 transcription complex. Cell. Mol. Immunol. 13, 47–56 (2016).

    Article  CAS  Google Scholar 

  3. Yasinska, I. M. et al. High mobility group box 1 (HMGB1) acts as an “alarmin” to promote acute myeloid leukaemia progression. OncoImmunology 7, e1438109 (2018).

    Article  Google Scholar 

  4. Goncalves Silva, I. et al. The tim-3-galectin-9 secretory pathway is involved in the immune escape of human acute myeloid leukemia cells. EBioMedicine 22, 44–57 (2017).

    Article  Google Scholar 

  5. Goncalves Silva, I. et al. The immune receptor Tim-3 acts as a trafficker in a Tim-3/galectin-9 autocrine loop in human myeloid leukemia cells. OncoImmunology 5, e1195535 (2016).

    Article  Google Scholar 

  6. Sumbayev, V. V. et al. Expression of functional neuronal receptor latrophilin 1 in human acute myeloid leukaemia cells. Oncotarget 7, 45575–45583 (2016).

    Article  Google Scholar 

  7. Maiga, A. et al. Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets. Blood Cancer J. 6, e431 (2016).

    Article  CAS  Google Scholar 

  8. Boucard, A. A., Maxeiner, S. & Sudhof, T. C. Latrophilins function as heterophilic cell-adhesion molecules by binding to teneurins: regulation by alternative splicing. J. Biol. Chem. 289, 387–402 (2014).

    Article  CAS  Google Scholar 

  9. Volynski, K. E. et al. Latrophilin, neurexin, and their signaling-deficient mutants facilitate α-latrotoxin insertion into membranes but are not involved in pore formation. J. Biol. Chem. 275, 41175–41183 (2000).

    Article  CAS  Google Scholar 

  10. Silva, J. P. et al. Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity transsynaptic receptor pair with signaling capabilities. Proc. Natl Acad. Sci. USA 108, 12113–12118 (2011).

    Article  CAS  Google Scholar 

  11. Yamaguchi, S. et al. FLRT2 and FLRT3 act as repulsive guidance cues for Unc5-positive neurons. EMBO J. 30, 2920–2933 (2011).

    Article  Google Scholar 

  12. Tabata, I., Ogita, F., Miyachi, M. & Shibayama, H. Effect of low blood glucose on plasma CRF, ACTH, and cortisol during prolonged physical exercise. J. Appl. Physiol. 71, 1807–1812 (1991).

    Article  CAS  Google Scholar 

Download references

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).

Author information

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

Authors
  1. Svetlana S. Sakhnevych
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Inna M. Yasinska
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alison M. Bratt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ouafa Benlaouer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Isabel Gonçalves Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rohanah Hussain
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giuliano Siligardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Walter Fiedler
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jasmin Wellbrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Bernhard F. Gibbs
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yuri A. Ushkaryov
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Vadim V. Sumbayev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vadim V. Sumbayev.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41423-018-0053-8

Keywords

This article is cited by

Search

Advanced search

Quick links