2021/05/11 by Naveen Sharma, Oluwatomisin T. Atolagbe, Zhongqi Ge +1 · 1 citation
Immunology and Microbiology · Medicine · #Immune Cell Function and Interaction #Immunotherapy and Immune Responses #CAR-T cell therapy research
paper · pdf · doi:10.1084/jem.20201811
openalex publication_date 2021/05/11 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
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.