IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v562y2018i7728d10.1038_s41586-018-0615-z.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    Binzhou Medical University)

  • Licai He

    (University of Texas Southwestern Medical Center
    Wenzhou Medical University)

  • Yuanzhi Chen

    (University of Texas Health Science Center
    Xiamen University)

  • Heyu Chen

    (University of Texas Southwestern Medical Center)

  • Weiguang Luo

    (University of Texas Southwestern Medical Center
    Central South University)

  • Zhigang Lu

    (University of Texas Southwestern Medical Center
    Fudan University)

  • Jingjing Xie

    (University of Texas Southwestern Medical Center
    Binzhou Medical University)

  • 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
    Central South University)

  • 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
    Xiamen University)

  • 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
    Central South University)

  • 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
    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)

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.

Suggested Citation

  • 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 , 2018. "LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration," Nature, Nature, vol. 562(7728), pages 605-609, October.
    • Handle: RePEc:nat:nature:v:562:y:2018:i:7728:d:10.1038_s41586-018-0615-z
    DOI: 10.1038/s41586-018-0615-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-018-0615-z
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-018-0615-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Takayoshi Matsumura & Haruhito Totani & Yoshitaka Gunji & Masahiro Fukuda & Rui Yokomori & Jianwen Deng & Malini Rethnam & Chong Yang & Tze King Tan & Tadayoshi Karasawa & Kazuomi Kario & Masafumi Tak, 2022. "A Myb enhancer-guided analysis of basophil and mast cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Hope Mumme & Beena E. Thomas & Swati S. Bhasin & Upaasana Krishnan & Bhakti Dwivedi & Pruthvi Perumalla & Debasree Sarkar & Gulay B. Ulukaya & Himalee S. Sabnis & Sunita I. Park & Deborah DeRyckere & , 2023. "Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

    More about this item

    Keywords

    Leukocyte Immunoglobulin-like Receptor B4 (LILRB4); Haematopoietic Stem/progenitor Cells (HSPCs); Microscale Thermophoresis (MST); CD28-coated Beads; Leukemia Infiltration;
    All these keywords.

    JEL classification:

    • B4 - Schools of Economic Thought and Methodology - - Economic Methodology

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:562:y:2018:i:7728:d:10.1038_s41586-018-0615-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.