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LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration
Nature ( IF 50.5 ) Pub Date : 2018-10-01 , DOI: 10.1038/s41586-018-0615-z
Mi Deng , Xun Gui , Jaehyup Kim , Li Xie , Weina Chen , Zunling Li , Licai He , Yuanzhi Chen , Heyu Chen , Weiguang Luo , Zhigang Lu , Jingjing Xie , Hywyn Churchill , Yixiang Xu , Zhan Zhou , Guojin Wu , Chenyi Yu , Samuel John , Kouyuki Hirayasu , Nam Nguyen , Xiaoye Liu , Fangfang Huang , Leike Li , Hui Deng , Haidong Tang , Ali H. Sadek , Lingbo Zhang , Tao Huang , Yizhou Zou , Benjamin Chen , Hong Zhu , Hisashi Arase , Ningshao Xia , Youxing Jiang , Robert Collins , M. James You , Jade Homsi , Nisha Unni , Cheryl Lewis , Guo-Qiang Chen , Yang-Xin Fu , X. Charlene Liao , Zhiqiang An , Junke Zheng , Ningyan Zhang , Cheng Cheng Zhang

Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia1. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML.The receptor LILRB4 on monocytic leukaemia cells suppresses T cell activity and support the infiltration of tumour cells into tissues.

中文翻译:

白血病细胞中的 LILRB4 信号传导介导 T 细胞抑制和肿瘤浸润

免疫检查点阻断疗法已成功治疗某些类型的癌症,但尚未显示出治疗白血病的临床益处1。这一结果表明白血病使用独特的机制来逃避这种治疗。正常免疫细胞表达的某些免疫抑制受体也存在于白血病细胞上。这些受体是否可以在肿瘤细胞中启动免疫相关的初级信号传导仍然未知。在这里,我们使用小鼠模型和人类细胞来证明 LILRB4,一种基于免疫受体酪氨酸的抑制基序受体和单核细胞白血病的标志物,支持肿瘤细胞浸润到组织中,并通过涉及 APOE、LILRB4 的信号通路抑制 T 细胞活性、SHP-2、uPAR 和 ARG1 在急性髓性白血病 (AML) 细胞中。LILRB4 的缺失或使用抗体阻断 LILRB4 信号会阻碍 AML 的发展。因此,LILRB4 通过创建免疫抑制微环境来协调单核细胞白血病细胞中的肿瘤侵袭途径。LILRB4 是治疗单核细胞 AML 的一个引人注目的靶点。单核细胞白血病细胞上的受体 LILRB4 抑制 T 细胞活性并支持肿瘤细胞向组织的浸润。
更新日期:2018-10-01
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