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

被引：252

作者：

Deng, Mi ^{[1
]}

Gui, Xun ^{[2
]}

Kim, Jaehyup ^{[3
]}

Xie, Li ^{[4
]}

Chen, Weina ^{[3
]}

Li, Zunling ^{[1
,5
]}

He, Licai ^{[1
,6
]}

Chen, Yuanzhi ^{[2
,7
]}

Chen, Heyu ^{[1
]}

Luo, Weiguang ^{[1
,8
]}

Lu, Zhigang ^{[1
,9
,10
]}

Xie, Jingjing ^{[1
,5
]}

Churchill, Hywyn ^{[3
]}

Xu, Yixiang ^{[2
]}

Zhou, Zhan ^{[1
]}

Wu, Guojin ^{[1
]}

Yu, Chenyi ^{[2
,11
]}

John, Samuel ^{[12
]}

Hirayasu, Kouyuki ^{[13
]}

Nam Nguyen ^{[1
]}

Liu, Xiaoye ^{[1
]}

Huang, Fangfang ^{[1
,14
]}

Li, Leike ^{[2
]}

Deng, Hui ^{[2
]}

Tang, Haidong ^{[3
]}

Sadek, Ali H. ^{[1
]}

Zhang, Lingbo ^{[1
,11
]}

Huang, Tao ^{[15
]}

Zou, Yizhou ^{[8
]}

Chen, Benjamin ^{[16
]}

Zhu, Hong ^{[17
,18
]}

Arase, Hisashi ^{[13
]}

Xia, Ningshao ^{[7
]}

Jiang, Youxing ^{[1
]}

Collins, Robert ^{[19
]}

You, M. James ^{[20
]}

Homsi, Jade ^{[19
]}

Unni, Nisha ^{[19
]}

Lewis, Cheryl ^{[18
]}

Chen, Guo-Qiang ^{[4
]}

Fu, Yang-Xin ^{[3
]}

Liao, X. Charlene ^{[15
]}

An, Zhiqiang ^{[2
]}

Zheng, Junke ^{[4
]}

Zhang, Ningyan ^{[2
]}

Zhang, Cheng Cheng ^{[1
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA

[2] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Brown Fdn Inst Mol Med, Texas Therapeut Inst, Houston, TX 77030 USA

[3] Univ Texas Southwestern Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA

[4] Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis, Dept Pathophysiol,Chinese Minist Educ, Shanghai, Peoples R China

[5] Binzhou Med Univ, Basic Med Sch, Taishan Immunol Program, Yantai, Peoples R China

[6] Wenzhou Med Univ, Sch Lab Med & Life Sci, Minist Educ, Key Lab Lab Med, Wenzhou, Peoples R China

[7] Xiamen Univ, Sch Publ Hlth, Xiamen, Peoples R China

[8] Cent S Univ, Xiangya Med Sch, Dept Immunol, Changsha, Peoples R China

[9] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China

[10] Fudan Univ, Peoples Hosp Shanghai 5, Shanghai, Peoples R China

[11] Cent S Univ, Xiangya Med Sch, Changsha, Hunan, Peoples R China

[12] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA

[13] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Res Inst Microbial Dis & Lab Immunochem, Dept Immunochem, Osaka, Japan

[14] Xiamen Univ, Zhongshan Hosp, Dept Hematol, Xiamen, Peoples R China

[15] Immune Onc Therapeut, Palo Alto, CA USA

[16] Univ Texas Southwestern Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA

[17] Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA

[18] Univ Texas Southwestern Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA

[19] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA

[20] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Div Pathol & Lab Med, Houston, TX 77030 USA

来源：

NATURE | 2018年 / 562卷 / 7728期

基金：

中国国家自然科学基金;

关键词：

HEMATOPOIETIC STEM-CELLS; ACUTE MYELOID-LEUKEMIA; NF-KAPPA-B; INHIBITORY RECEPTOR ILT3; IN-VIVO; IMMUNE PRIVILEGE; MICE; EXPRESSION; CANCER; TRANSPLANTATION;

D O I：

10.1038/s41586-018-0615-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

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 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.

引用

页码：605 / +

页数：28

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