| RRC ID |
67797
|
| 著者 |
Izumi K, Shindo T, Ngo HT, Nakayama-Hosoya K, Akahane K, Tamai M, Nguyen TTT, Kawana-Tachikawa A, Inukai T, Takaori-Kondo A.
|
| タイトル |
KIR3DL1 Allotype-Dependent Modulation of NK Cell Immunity against Chronic Myeloid Leukemia.
|
| ジャーナル |
Immunohorizons
|
| Abstract |
Tyrosine kinase inhibitor (TKI)-treated chronic myeloid leukemia (CML) patients with increased NK cell number have a better prognosis, and thus, NK cells may suppress CML. However, the efficacy of TKIs varies for reasons yet to be fully elucidated. As NK cell activity is modulated by interactions between their killer cell Ig-like receptors (KIRs) and HLAs of target cells, the combination of their polymorphisms may have functional significance. We previously showed that allelic polymorphisms of KIR3DL1 and HLAs were associated with the prognosis of TKI-treated CML patients. In this study, we focus on differential NK cell activity modulation through KIR3DL1 allotypes. KIR3DL1 expression levels varied according to their alleles. The combination of KIR3DL1 expression level and HLA-Bw4 motifs defined NK cell activity in response to the CML-derived K562 cell line, and Ab-mediated KIR3DL1 blocking reversed this activity. The TKI dasatinib enhanced NK cell activation and cytotoxicity in a KIR3DL1 allotype-dependent manner but did not significantly decrease effector regulatory T cells, suggesting that it directly activated NK cells. Dasatinib also enhanced NK cell cytotoxicity against K562 bearing the BCR-ABL1 T315I TKI resistance-conferring mutation, depending on KIR3DL1/HLA-Bw4 allotypes. Transduction of KIR3DL1*01502 into the NK cell line NK-92 resulted in KIR3DL1 expression and suppression of NK-92 activity by HLA-B ligation, which was reversed by anti-KIR3DL1 Ab. Finally, KIR3DL1 expression levels also defined activation patterns in CML patient-derived NK cells. Our findings raise the possibility of a novel strategy to enhance antitumor NK cell immunity against CML in a KIR3DL1 allotype-dependent manner.
|
| 巻・号 |
5(8)
|
| ページ |
687-702
|
| 公開日 |
2021-8-25
|
| DOI |
10.4049/immunohorizons.2100054
|
| PII |
immunohorizons.2100054
|
| PMID |
34433624
|
| MeSH |
Alleles
Cell Line, Tumor
Cytotoxicity, Immunologic / drug effects
Cytotoxicity, Immunologic / genetics
Cytotoxicity, Immunologic / immunology
Dasatinib / pharmacology
Fusion Proteins, bcr-abl / genetics
Fusion Proteins, bcr-abl / immunology
Gene Expression Regulation, Leukemic / drug effects
Gene Expression Regulation, Leukemic / genetics
Gene Expression Regulation, Leukemic / immunology*
HLA-B Antigens / genetics
HLA-B Antigens / immunology
HLA-B Antigens / metabolism
Humans
K562 Cells
Killer Cells, Natural / drug effects
Killer Cells, Natural / immunology*
Killer Cells, Natural / metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology*
Lymphocyte Activation / drug effects
Lymphocyte Activation / genetics
Lymphocyte Activation / immunology
Mutation
Protein Kinase Inhibitors / pharmacology
Receptors, KIR3DL1 / genetics
Receptors, KIR3DL1 / immunology*
Receptors, KIR3DL1 / metabolism
|
| リソース情報 |
| ヒト・動物細胞 |
K562(RCB1897) |
