UTHealth Houston and UTSW researchers discovered that LILRB3 stimulates NF-κB signaling and enhances acute myeloid leukemia (AML) cells. They generated a panel of novel anti-LILRB3 monoclonal antibodies (mAbs), which exhibited increasing killing of leukemia cells and promoting cytotoxic T cell activity against tumors.
Background
Leukocyte immunoglobulin-like receptor B (LILRB), a family of immune checkpoint receptors, contributes to acute myeloid leukemia (AML) development, but the specific mechanisms triggered by activation or inhibition of these immune checkpoints in cancer is largely unknown. LILRB3 is a member of LILRB family that is restrictively expressed in myeloid cells. LILRB3 contains four cytoplasmic ITIM motifs and contributes to negative regulation of immune response. However, the ligand and function of LILRB3 are little known.
Significance and Impact
Researchers at UTHealth Houston and The University of Texas Southwestern Medical Center (UTSW) discovered that activated LILRB3 in AML cells recruits CFIP and subsequently upregulates NF-Κb, which results in enhanced leukemic cell survival and inhibition of T-cell-mediated anti-tumor activity. They then developed novel anti-LILRB3 mAbs and demonstrated that blockade of LILRB3 signaling with antagonizing anti-LILRB3 mAbs hampers AML progression in vivo. These results indicate anti-LILRB3 mAbs may be an attractive immunotherapy to AML patients.
Benefits/Technology Advantages
Related Publications
Wu, Guojin, et al. "LILRB3 supports acute myeloid leukemia development and regulates T-cell antitumor immune responses through the TRAF2–cFLIP–NF-κB signaling axis." Nature cancer 2.11 (2021): 1170-1184.