LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy

J Exp Med. 2021 Jul 5;218(7):e20201811. doi: 10.1084/jem.20201811. Epub 2021 May 11.


Immune receptors expressed on TAMs are intriguing targets for tumor immunotherapy. In this study, we found inhibitory receptor LILRB4 on a variety of intratumoral immune cell types in murine tumor models and human cancers, most prominently on TAMs. LILRB4, known as gp49B in mice, is a LILRB family receptor. Human and murine LILRB4 have two extracellular domains but differ in the number of intracellular ITIMs (three versus two). We observed a high correlation in LILRB4 expression with other immune inhibitory receptors. After tumor challenge, LILRB4-/- mice and mice treated with anti-LILRB4 antibody showed reduced tumor burden and increased survival. LILRB4-/- genotype or LILRB4 blockade increased tumor immune infiltrates and the effector (Teff) to regulatory (Treg) T cell ratio and modulated phenotypes of TAMs toward less suppressive, CD4+ T cells to Th1 effector, and CD8+ T cells to less exhausted. These findings reveal that LILRB4 strongly suppresses tumor immunity in TME and that alleviating that suppression provides antitumor efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cell Movement / immunology
  • Humans
  • Immunotherapy / methods
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Receptors, Immunologic / immunology*
  • T-Lymphocytes, Regulatory / immunology


  • LILRB4 protein, human
  • Membrane Glycoproteins
  • Receptors, Immunologic