KIR3DL1 Allotype-Dependent Modulation of NK Cell Immunity against Chronic Myeloid Leukemia

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

慢性骨髄性白血病に対するNK細胞免疫のKIR3DL1アロタイプに基づく調節

京都大学新制・課程博士博士(医学)甲第23775号医博第4821号新制||医||1057(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 河本 宏, 教授 永井 純正, 教授 濵﨑 洋子学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Formal Nucleophilic Boryl Substitution of Organic Halides with Silylborane/Alkoxy Base System

Boryl substitution of organohalides with a silylborane and alkoxy bases is described. This reaction can be applied to various functionalized aryl halides. Alkyl and alkenyl halides, and even sterically congested aryl bromides also provided the corresponding borylated products in high yields. Mechanistic studies indicated that neither trace transition-metal impurities nor aryl radical species involved in this reaction

Teaching a Tele-robot using Natural Language Commands

For Internet-based tele operation systems, user-friendly natural interfaces are advantageous because those systems are intended to be used by non-experts. In developing user friendly interfaces, natural language communication is mandatory. This paper presents a system in which a sub-set of natural language is used to command a tele-robot manipulator doing an object sorting task. The paper discusses about referring to objects with natural language commands such as "pick the small red cube". This is achieved by learning individual lexical symbols that refer to colors, shapes, and sizes independently, and then inferring the meaning of a combination of them