LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration

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 () and Cheng Cheng Zhang ()
Additional contact information
Mi Deng: University of Texas Southwestern Medical Center
Xun Gui: University of Texas Health Science Center
Jaehyup Kim: University of Texas Southwestern Medical Center
Li Xie: Shanghai Jiao Tong University School of Medicine
Weina Chen: University of Texas Southwestern Medical Center
Zunling Li: University of Texas Southwestern Medical Center
Licai He: University of Texas Southwestern Medical Center
Yuanzhi Chen: University of Texas Health Science Center
Heyu Chen: University of Texas Southwestern Medical Center
Weiguang Luo: University of Texas Southwestern Medical Center
Zhigang Lu: University of Texas Southwestern Medical Center
Jingjing Xie: University of Texas Southwestern Medical Center
Hywyn Churchill: University of Texas Southwestern Medical Center
Yixiang Xu: University of Texas Health Science Center
Zhan Zhou: University of Texas Southwestern Medical Center
Guojin Wu: University of Texas Southwestern Medical Center
Chenyi Yu: University of Texas Health Science Center
Samuel John: University of Texas Southwestern Medical Center
Kouyuki Hirayasu: Osaka University
Nam Nguyen: University of Texas Southwestern Medical Center
Xiaoye Liu: University of Texas Southwestern Medical Center
Fangfang Huang: University of Texas Southwestern Medical Center
Leike Li: University of Texas Health Science Center
Hui Deng: University of Texas Health Science Center
Haidong Tang: University of Texas Southwestern Medical Center
Ali H. Sadek: University of Texas Southwestern Medical Center
Lingbo Zhang: University of Texas Southwestern Medical Center
Tao Huang: Immune-Onc Therapeutics, Inc.
Yizhou Zou: Central South University
Benjamin Chen: University of Texas Southwestern Medical Center
Hong Zhu: University of Texas Southwestern Medical Center
Hisashi Arase: Osaka University
Ningshao Xia: Xiamen University
Youxing Jiang: University of Texas Southwestern Medical Center
Robert Collins: University of Texas Southwestern Medical Center
M. James You: The University of Texas MD Anderson Cancer Center
Jade Homsi: University of Texas Southwestern Medical Center
Nisha Unni: University of Texas Southwestern Medical Center
Cheryl Lewis: University of Texas Southwestern Medical Center
Guo-Qiang Chen: Shanghai Jiao Tong University School of Medicine
Yang-Xin Fu: University of Texas Southwestern Medical Center
X. Charlene Liao: Immune-Onc Therapeutics, Inc.
Zhiqiang An: University of Texas Health Science Center
Junke Zheng: Shanghai Jiao Tong University School of Medicine
Ningyan Zhang: University of Texas Health Science Center
Cheng Cheng Zhang: University of Texas Southwestern Medical Center

Nature, 2018, vol. 562, issue 7728, 605-609

Abstract: Abstract 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.

Keywords: Leukocyte Immunoglobulin-like Receptor B4 (LILRB4); Haematopoietic Stem/progenitor Cells (HSPCs); Microscale Thermophoresis (MST); CD28-coated Beads; Leukemia Infiltration (search for similar items in EconPapers)
Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (2)

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DOI: 10.1038/s41586-018-0615-z

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