LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration
Mi Deng,Xun Gui,Jaehyup Kim,Li Xie,Weina Chen,Zunling Li,Zunling Li,Licai He,Licai He,Yuanzhi Chen,Yuanzhi Chen,Heyu Chen,Weiguang Luo,Weiguang Luo,Zhigang Lu,Zhigang Lu,Jingjing Xie,Jingjing Xie,Hywyn Churchill,Yixiang Xu,Zhan Zhou,Guojin Wu,Chenyi Yu,Chenyi Yu,Samuel John,Kouyuki Hirayasu,Nam X. Nguyen,Xiaoye Liu,Fangfang Huang,Fangfang Huang,Leike Li,Hui Deng,Haidong Tang,Ali H. Sadek,Lingbo Zhang,Lingbo Zhang,Tao Huang,Yizhou Zou,Benjamin P C Chen,Hong Zhu,Hisashi Arase,Ningshao Xia,Youxing Jiang,Robert H. Collins,M. James You,Jade Homsi,Nisha Unni,Cheryl M. Lewis,Guo-Qiang Chen,Yang Xin Fu,X. Charlene Liao,Zhiqiang An,Junke Zheng,Ningyan Zhang,Cheng Cheng Zhang +54 more
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TLDR
It is shown 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, LIL RB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemis (AML) cells.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.read more
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