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 NguyenXiaoye 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, Chengcheng Zhang

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)605-609
Number of pages5
JournalNature
Volume562
Issue number7728
DOIs
StatePublished - Oct 25 2018

ASJC Scopus subject areas

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    Deng, M., Gui, X., Kim, J., Xie, L., Chen, W., Li, Z., He, L., Chen, Y., Chen, H., Luo, W., Lu, Z., Xie, J., Churchill, H., Xu, Y., Zhou, Z., Wu, G., Yu, C., John, S., Hirayasu, K., ... Zhang, C. (2018). LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration. Nature, 562(7728), 605-609. https://doi.org/10.1038/s41586-018-0615-z