Cancer Immunology, Immunotherapy

, Volume 61, Issue 2, pp 193–202 | Cite as

The immune inhibitory receptor osteoactivin is upregulated in monocyte-derived dendritic cells by BCR–ABL tyrosine kinase inhibitors

  • Mark-Alexander Schwarzbich
  • Michael Gutknecht
  • Julia Salih
  • Helmut R. Salih
  • Peter Brossart
  • Susanne M. Rittig
  • Frank Grünebach
Original article


Multiple approaches presently aim to combine targeted therapies using tyrosine kinase inhibitors with immunotherapy. Ex vivo-generated dendritic cells are frequently used in such strategies due to their unique ability to initiate primary T-cell immune responses. Besides governing tumor cell growth, many kinases targeted by tyrosine kinase inhibitors are involved in the development and function of dendritic cells and thus tyrosine kinase inhibitor therapy may cause immunoinhibitory side effects. We here report that exposure of developing human monocyte-derived dendritic cells to the BCR–ABL inhibitors imatinib, dasatinib, and nilotinib results in profound upregulation of the transmembrane glycoprotein osteoactivin that has recently been characterized as a negative regulator of T-cell activation. Thus, in line with osteoactivin upregulation, exposure to tyrosine kinase inhibitors resulted in significantly reduced stimulatory capacity of dendritic cells in mixed lymphocyte reactions that could be restored by the addition of blocking anti-osteoactivin antibody. Our data demonstrate that tyrosine kinase inhibitor-mediated inhibition of dendritic cell function is, at least in great part, mediated by upregulation of the immune inhibitory molecule osteoactivin.


Dendritic cells Immunotherapy Tyrosine kinase inhibitors Immune inhibitory receptor 



This work was supported by Deutsche Krebshilfe (project no. 109046) and SFB 685. S. M. Rittig is supported by the European Social Fund in Baden-Württemberg. We thank Sylvia Stephan for excellent technical assistance.

Supplementary material

262_2011_1096_MOESM1_ESM.pdf (107 kb)
Supplementary material 1 (PDF 106 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Mark-Alexander Schwarzbich
    • 1
  • Michael Gutknecht
    • 1
  • Julia Salih
    • 1
  • Helmut R. Salih
    • 1
  • Peter Brossart
    • 2
  • Susanne M. Rittig
    • 1
  • Frank Grünebach
    • 1
  1. 1.Department of Oncology, Hematology, Immunology, Rheumatology and PulmologyUniversity of TübingenTübingenGermany
  2. 2.Department of Hematology and OncologyUniversity of BonnBonnGermany

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