Therapeutic Strategies to Target LILRB Receptors on Myeloid Cells for Cancer Immunotherapy
type: CreativeWork
description: The existing T cell-centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells which inhibit anti-tumor immunity are recognized as one of the major obstacles in cancer treatment. LILRB3 and LILRB4, immune inhibitory receptors containing tyrosine-based inhibitory motifs (ITIMs), are expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor to support the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the immune system to treat solid cancers. Furthermore, it is unknown whether anti-LILRB4 CAR-T cells can be redirected against other types of cancers. We found that galectin-4 and galectin-7 induce activation of LILRB3 and that LILRB3 is functionally expressed on immunosuppressive myeloid cells. In some samples from patients with solid cancers, blockade of LILRB3 signaling by an antagonistic antibody inhibited the activity of immunosuppressive myeloid cells. Anti-LILRB3 antibody also impeded tumor development in myeloid-specific LILRB3 transgenic mice through a T cell-dependent manner. In addition, it was found that switch proteins could activate anti-LILRB4 CAR-T cells against LILRB4- cancers. LILRB3 blockade and redirection of anti-LILRB4 CAR-T cells may prove to be novel approaches for immunotherapy of both solid and hematologic cancers.
abstract: The existing T cell-centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells which inhibit anti-tumor immunity are recognized as one of the major obstacles in cancer treatment. LILRB3 and LILRB4, immune inhibitory receptors containing tyrosine-based inhibitory motifs (ITIMs), are expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor to support the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the immune system to treat solid cancers. Furthermore, it is unknown whether anti-LILRB4 CAR-T cells can be redirected against other types of cancers. We found that galectin-4 and galectin-7 induce activation of LILRB3 and that LILRB3 is functionally expressed on immunosuppressive myeloid cells. In some samples from patients with solid cancers, blockade of LILRB3 signaling by an antagonistic antibody inhibited the activity of immunosuppressive myeloid cells. Anti-LILRB3 antibody also impeded tumor development in myeloid-specific LILRB3 transgenic mice through a T cell-dependent manner. In addition, it was found that switch proteins could activate anti-LILRB4 CAR-T cells against LILRB4- cancers. LILRB3 blockade and redirection of anti-LILRB4 CAR-T cells may prove to be novel approaches for immunotherapy of both solid and hematologic cancers.
author: Huang, Ryan Shie
language: en
keywords: Myeloid Cells, Myeloid-Derived Suppressor Cells, Neoplasms, Receptors, Immunologic, Antigens, CD
date published: 2026-06-15T19:42:34Z
date modified: 2026-07-24T05:52:38Z
provider: University of Texas Southwestern Medical Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Texas Southwestern Medical Center

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2152.5/10806