NK cells play a significant role in immunosurveillance at the early stage of MLL-AF9 acute myeloid leukemia via CD226/CD155 interactions
NK cells play a significant role in immunosurveillance at the early stage of MLL-AF9 acute myeloid leukemia via CD226/CD155 interactions
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NK 细胞通过 CD226/CD155 相互作用在 MLL-AF9 急性髓系白血病早期的免疫监视中发挥重要作用
DOI：
10.1007/s11427-015-4968-3
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Hao Sha
中科院分区：
文献类型：
--
作者：
Wang YaJie;Chen Chen;Dong Fang;Ma ShiHui;Xu Jing;Gong YueMin;Cheng Hui;Zhou Yuan;Cheng Tao;Hao Sha
急性髓性白血病（AML）是一种侵袭性血液恶性肿瘤，免疫系统参与白血病发展的机制尚不清楚。在本研究中，我们利用了髓系/淋巴系或混合系白血病;易位至3（MLLT 3/MLL-AF 9）诱导的AML小鼠模型，有或没有暴露于辐射。我们发现，白血病细胞可以在免疫系统完整的宿主中存活和扩增，而免疫系统受损的小鼠中白血病进展加快。此外，白血病细胞通过编辑其免疫原性，包括上调抑制性抗原（即，CD 47）和活性抗原的下调（即，CD 86、CD 54、视黄酸早期转录物（RAE）、组织相容性2、D区基因座B（H2-DB）和H2-Dd）。自然杀伤（NK）细胞在AML进展的早期阶段被激活，而T细胞在晚期阶段被刺激。此外，NK细胞耗竭表明，NK细胞是消除我们的AML小鼠模型中的白血病细胞所必需的。值得注意的是，CD 155/CD 226主要介导NK细胞和白血病细胞之间的相互作用，并在AML的早期阶段促进NK细胞的抗肿瘤作用。来自不同血液恶性肿瘤患者的临床数据显示，CD 155表达在血液恶性肿瘤中降低。综上所述，我们的结果表明，NK细胞在AML早期阶段主要通过CD 226/CD 155相互作用对白血病细胞的免疫监视中起着关键作用;然而，NK细胞不足以消除白血病细胞。
Acute myeloid leukemia (AML) is an aggressive hematological malignancy, and the mechanism underlying immune system involvement in leukemia development is unclear. In the present study, we utilized a myeloid/lymphoid or mixed-lineage leukemia; translocated to, 3 (MLLT3/MLL-AF9)-induced AML mouse model with or without exposure to irradiation. We found that the leukemia cells could survive and expand in hosts with intact immune systems, whereas leukemia progression was accelerated in mice with impaired immune systems. Moreover, the leukemia cells escaped from host immunosurveillance via editing their immunogenicity, including the up-regulation of an inhibitory antigen (i.e., CD47) and the down-regulation of active antigens (i.e., CD86, CD54, retinoic acid early transcript (RAE), histocompatibility 2, D region locus b (H2-Db) and H2-Dd). Natural killer (NK) cells were activated in the early phase of AML progression, whereas T cells were stimulated in the late phase. Furthermore, NK cell depletion showed that NK cells were necessary for the elimination of leukemia cells in our AML mouse model. Notably, CD155/CD226 primarily mediated the interaction between NK cells and leukemia cells and contributed to the antitumor effects of NK cells during the early phase of AML. Clinical data from patients with diverse hematological malignancies showed that CD155 expression was decreased in hematological malignancies. Taken together, our results demonstrate that NK cells play a pivotal role in immunosurveillance against leukemia cells during the early stage of AML primarily through the CD226/CD155 interaction; however, NK cells are not sufficient to eliminate leukemia cells.
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影响因子：
6.4
作者：
Buss, Eike C.;Ho, Anthony D.
通讯作者：
Ho, Anthony D.
急性髓系白血病的免疫治疗
影响因子：
4.7
作者：
J. Jurcic
通讯作者：
J. Jurcic
影响因子：
20.3
作者：
G. Marotta;V. Zagonel;A. Pinto
通讯作者：
G. Marotta;V. Zagonel;A. Pinto
影响因子：
2.5
作者：
N. Shimura;S. Kojima
通讯作者：
N. Shimura;S. Kojima
DOI：
10.1016/s0140-6736(85)92916-2
发表时间：
1985-05
期刊：
The Lancet
影响因子：
--
作者：
T. Büchner;D. Urbanitz;H. Rühl;J. Fischer;R. Kuse
通讯作者：
T. Büchner;D. Urbanitz;H. Rühl;J. Fischer;R. Kuse