First Author | Sharma N | Year | 2021 |
Journal | J Exp Med | Volume | 218 |
Issue | 7 | PubMed ID | 33974041 |
Mgi Jnum | J:322185 | Mgi Id | MGI:6724859 |
Doi | 10.1084/jem.20201811 | Citation | Sharma N, et al. (2021) LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy. J Exp Med 218(7) |
abstractText | 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. |