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.

  • Letter to the Editor
  • Published:

Cotransplantation of mesenchymal cells and a higher relapse rate: a role for HLA-G molecules?

Leukemia volume 22, page 2273 (2008)Cite this article

We have read with interest the paper by Ning et al.1 reporting a correlation between the cotransplantation of mesenchymal stem cells (MSCs) in allogeneic haemapoietic stem cell transplantation and a higher recurrence rate of malignant haematologic diseases. The authors concluded their paper by suggesting that ‘the use of MSCs must be handled with extreme caution before a large-scale trial is performed’. Recently, several studies have reported the ability of MSCs, when co-cultured with activated peripheral blood mononuclear cells or directly activated by exogenous Interleukin 10, to modulate membrane bound and soluble human leukocyte antigen-G (HLA-G) antigens.2, 3, 4 HLA-G antigens are nonclassical HLA-class I molecules characterized by tolerogenic and anti-inflammatory functions. In particular, both membrane and soluble HLA-G molecules have been demonstrated to inhibit Natural killer and CD8+ T cell mediated cytolysis, CD4+ T lymphocyte proliferation and dendritic cell maturation. Furthermore, the expression of HLA-G antigens has been associated with the induction of regulatory T cells.4 Overall, it is currently accepted that HLA-G molecules, by direct and indirect mechanisms, can inhibit innate and adaptive immune responses. The production of sHLA-G molecules by MSCs2, 3, 4 has suggested, in addition to other mechanisms, a rationale for the immunomodulatory properties of MSCs in preventing graft versus host disease (GVHD).

Several researches have demonstrated that HLA-G modulation represents a beneficial event in organ transplantations, autoimmune diseases and pregnancy where the downregulation of the immune response is essential for a positive outcome. In contrast, the presence of HLA-G antigens has been associated with clinical negative consequences in cancer and viral infections where the tolerogenic function of these molecules permits the mutated/infected cells to avoid the innate and adaptive immune responses. In particular, the HLA-G expression by cancer tissues and the relationship between plasma sHLA-G levels and cancer development5, 6, 7, 8 confirm the role of HLA-G molecules in sustaining the immune escape of cancer cells.

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

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

References

  1. Ning H, Yang F, HU L, Feng K, Zhang J, Yu Z et al. The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in heamatological malignancy patients: outcome of a pilot clinical study. Leukemia 2008; 22: 593–599.

    Article  CAS  PubMed  Google Scholar 

  2. Rizzo R, Campioni D, Stignani M, Bagnara GP, Bonsi L, Alviano F et al. A functional role for soluble HLA-G antigens in immune modulation mediated by mesenchymal stromal cells. Cytotherapy 2008, (in press).

  3. Nasef A, Mathieu N, Chapel A, Frick J, François S, Mazurier C et al. Immunosuppressive effects of mesenchymal stem cells: involvement of HLA-G. Transplantation 2007; 84: 231–237.

    Article  CAS  PubMed  Google Scholar 

  4. Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25 high FOXP3+ regulatory T cells. Stem Cells 2008; 26: 212–222.

    Article  CAS  PubMed  Google Scholar 

  5. Nückel H, Rebmann V, Dürig J, Dührsen U, Grosse-Wilde H . HLA-G expression is associated with an unfavorable outcome and immunodeficiency in chronic lymphocytic leukemia. Blood 2005; 105: 1694–1698.

    Article  PubMed  Google Scholar 

  6. Urosevic M, Dummer R . Human leukocyte antigen-G and cancer immunoediting. Cancer Res 2008; 68: 627–630.

    Article  CAS  PubMed  Google Scholar 

  7. Rouas-Freiss N, Moreau P, Menier C, LeMaoult J, Carosella ED . Expression of tolerogenic HLA-G molecules in cancer prevents antitumor responses. Semin Cancer Biol 2007; 17: 413–421.

    Article  CAS  PubMed  Google Scholar 

  8. Pistoia V, Morandi F, Wang X, Ferrone S . Soluble HLA-G: are they clinically relevant? Semin Cancer Biol 2007; 17: 469–479.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental and Diagnostic Medicine, Laboratory of Immunogenetics, Section of Medical Genetics, University of Ferrara, Ferrara, Italy

    R Rizzo & O R Baricordi

  2. Department of Biomedical Sciences and Advanced Therapies, Hematology Section, Azienda Ospedaliera-Universitaria Arcispedale S. Anna, Ferrara, Italy

    D Campioni & F Lanza

Authors
  1. R Rizzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D Campioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F Lanza
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O R Baricordi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R Rizzo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rizzo, R., Campioni, D., Lanza, F. et al. Cotransplantation of mesenchymal cells and a higher relapse rate: a role for HLA-G molecules?. Leukemia 22, 2273 (2008). https://doi.org/10.1038/leu.2008.135

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2008.135

Search

Advanced search

Quick links