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作者

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. Nguyen, N. Liu, X. Huang, F. Li, L. Deng, H. Tang, H. Sadek, A.H. Zhang, L. Huang, T. Zou, Y. Chen, B. Zhu, H. Arase, H. Xia, N. Jiang, Y. Collins, R. You, M.J. Homsi, J. Unni, N. Lewis, C. Chen, G.-Q. Fu, Y.-X. Liao, X.C. An, Z. Zheng, J. Zhang, N. Zhang, C.C.

作者单位

p Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States m Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, China g School of Public Health, Xiamen University, Xiamen, China r Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States h Department of Immunology, Xiangya Medical School, Central South University, Changsha, China s Department of Hematopathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States n Immune-Onc Therapeutics, Inc., Palo Alto, CA, United States j Xiangya Medical School, Central South University, Changsha, China a Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, United States i Institute of Biomedical Sciences and the Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, China Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States f Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medical and Life Science, Wenzhou Medical University, Wenzhou, China o Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, United States q Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States Taishan Immunology Program, Basic Medicine School, Binzhou Medical University, Yantai, China Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States l Department of Immunochemistry, Research Institute for Microbial Diseases and Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China k Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States

刊名

Nature

年份

2018

卷号

Vol.562 No.7728

页码

605-609

ISSN

0028-0836;1476-4687

摘要

Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia 1 . 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 sh...更多

Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia 1 . 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 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.收起

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