B-lymphoma cells escape rituximab-triggered elimination by NK cells through increased HLA class I expression.
Abstract | OBJECTIVE: Antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells is a major effector mechanism of the monoclonal anti-CD20 antibody rituximab in eliminating B-cell lymphomas. Resistance to this treatment occurs, although CD20 antigen is expressed on the tumor cells. MATERIALS AND METHODS: RESULTS: HLA, but not CD20 expression density correlated with NK-cell activity against rituximab-labeled targets. ADCC was increased or decreased following HLA shielding or KIR activation by anti-KIR antibodies, respectively. Herein we show that rituximab-induced ADCC is attenuated upon ligation of KIR by HLA molecules expressed on human B- lymphoma target cells. Moreover, anti-KIR antibodies do not only block KIR/HLA interactions, but display agonistic effects at the KIR, which has to be considered for therapeutical applications. CONCLUSION: KIR activation and HLA expression density are critical determinants for the efficacy of rituximab treatment. An explanation for the failure of rituximab treatment may be the protection of the tumor cells from ADCC by inhibiting NK-cell function with their surface HLA.
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Authors | Andrea Borgerding, Justin Hasenkamp, Michael Engelke, Nina Burkhart, Lorenz Trümper, Jürgen Wienands, Bertram Glass |
Journal | Experimental hematology
(Exp Hematol)
Vol. 38
Issue 3
Pg. 213-21
(Mar 2010)
ISSN: 1873-2399 [Electronic] Netherlands |
PMID | 20056126
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Murine-Derived
- Antigens, CD20
- Antineoplastic Agents
- HLA-C Antigens
- Histocompatibility Antigens Class I
- KIR2DL1 protein, human
- KIR2DL2 protein, human
- KIR2DL3 protein, human
- Receptors, KIR
- Receptors, KIR2DL1
- Receptors, KIR2DL2
- Receptors, KIR2DL3
- Rituximab
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Topics |
- Antibodies, Monoclonal
(pharmacology)
- Antibodies, Monoclonal, Murine-Derived
- Antibody-Dependent Cell Cytotoxicity
(drug effects, immunology)
- Antigens, CD20
(immunology, metabolism)
- Antineoplastic Agents
(pharmacology)
- Cell Line
- Cell Line, Tumor
- Cells, Cultured
- Dose-Response Relationship, Drug
- Enzyme-Linked Immunosorbent Assay
- Flow Cytometry
- HLA-C Antigens
(metabolism)
- Histocompatibility Antigens Class I
(metabolism)
- Humans
- K562 Cells
- Killer Cells, Natural
(immunology, metabolism)
- Lymphocyte Activation
(drug effects, immunology)
- Lymphocytes
(drug effects, immunology, metabolism)
- Lymphoma, B-Cell
(immunology, metabolism, pathology)
- Receptors, KIR
(immunology, metabolism)
- Receptors, KIR2DL1
(immunology, metabolism)
- Receptors, KIR2DL2
(immunology, metabolism)
- Receptors, KIR2DL3
(immunology, metabolism)
- Rituximab
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