The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells
| Autor: | Graham P. Cook, Yasser M. El-Sherbiny, Stephen J. Richards, Sylvia Feyler, Tim D. Holmes, Ann W. Morgan, Dennis McGonagle, Faith E. Davies, Gareth J. Morgan, Sarah L. Mackie, Josephine L. Meade, Gordon Cook |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Antigens Differentiation T-Lymphocyte Cytotoxicity Immunologic Cancer Research NK Cell Lectin-Like Receptor Subfamily K CD226 Bone Marrow Cells Biology Natural killer cell immune system diseases hemic and lymphatic diseases medicine Humans CD155 Receptors Immunologic Multiple myeloma Aged Aged 80 and over Natural Cytotoxicity Triggering Receptor 1 Middle Aged NKG2D medicine.disease Killer Cells Natural medicine.anatomical_structure Oncology Immunology Cancer research biology.protein Receptors Natural Killer Cell Multiple Myeloma Poliovirus Receptor |
| Zdroj: | Cancer research. 67(18) |
| ISSN: | 0008-5472 |
| Popis: | Recent evidence suggests a role for natural killer (NK) cells in the control of multiple myeloma. We show that expression of the NK cell receptor DNAM-1 (CD226) is reduced on CD56dim NK cells from myeloma patients with active disease compared with patients in remission and healthy controls. This suggested that this receptor might play a role in NK-myeloma interactions. The DNAM-1 ligands Nectin-2 (CD112) and the poliovirus receptor (PVR; CD155) were expressed by most patient myeloma samples analyzed. NK killing of patient-derived myelomas expressing PVR and/or Nectin-2 was DNAM-1 dependent, revealing a functional role for DNAM-1 in myeloma cell killing. In myeloma cell lines, cell surface expression of PVR was associated with low levels of NKG2D ligands, whereas cells expressing high levels of NKG2D ligands did not express PVR protein or mRNA. Furthermore, NK cell-mediated killing of myeloma cell lines was dependent on either DNAM-1 or NKG2D but not both molecules. In contrast, the natural cytotoxicity receptor NKp46 was required for the killing of all myeloma cell lines analyzed. Thus, DNAM-1 is important in the NK cell-mediated killing of myeloma cells expressing the cognate ligands. The importance of NKp46, NKG2D, and DNAM-1 in myeloma killing mirrors the differential expression of NK cell ligands by myeloma cells, reflecting immune selection during myeloma disease progression. [Cancer Res 2007;67(18):8444–9] |
| Databáze: | OpenAIRE |
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