The immune inhibitory receptor osteoactivin is upregulated in monocyte-derived dendritic cells by BCR–ABL tyrosine kinase inhibitors
| Autor: | Mark-Alexander Schwarzbich, Helmut R. Salih, Julia Salih, Frank Grünebach, Michael Gutknecht, Susanne M Rittig, Peter Brossart |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
medicine.drug_class T-Lymphocytes Immunology PTK2 Dasatinib Fusion Proteins bcr-abl Lymphocyte Activation Tropomyosin receptor kinase C Piperazines Receptor tyrosine kinase Tyrosine-kinase inhibitor medicine Humans Immunology and Allergy Molecular Targeted Therapy Cells Cultured Membrane Glycoproteins biology Antibodies Monoclonal Dendritic Cells Protein-Tyrosine Kinases Up-Regulation Cell biology Thiazoles Pyrimidines Oncology Benzamides ROR1 Imatinib Mesylate Cancer research biology.protein Immunotherapy Lymphocyte Culture Test Mixed Tyrosine kinase Platelet-derived growth factor receptor Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Cancer Immunology, Immunotherapy. 61:193-202 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-011-1096-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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