LILRB3 Supports Immunosuppressive Activity of Myeloid Cells and Tumor Development

Authors

Ryan Huang
Xiaoye Liu
Jaehyup Kim
Hui Deng
Mi Deng
Xun Gui
Heyu Chen
Guojin Wu
Wei Xiong
Jingjing Xie
Cheryl Lewis
Jade Homsi
Xing Yang
Chengcheng Zhang
Yubo He
Qi Lou
Caroline Smith
Samuel John
Ningyan Zhang
Zhiqiang An
Cheng Cheng Zhang

Publication Date

3-4-2024

Journal

Cancer Immunology Resesarch

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, including myeloid-derived suppressor cells (MDSC), that inhibit antitumor immunity and support multiple steps of tumor development are recognized as one of the major obstacles in cancer treatment. Leukocyte Ig-like receptor subfamily B3 (LILRB3), an immune inhibitory receptor containing tyrosine-based inhibitory motifs (ITIM), is expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor in regulating the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the immune system to treat solid tumors. Here, we report 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 also impeded tumor development in myeloid-specific LILRB3 transgenic mice through a T cell-dependent manner. LILRB3 blockade may prove to be a novel approach for immunotherapy of solid cancers.

Keywords

Mice, Animals, Humans, Myeloid Cells, Neoplasms, Myeloid-Derived Suppressor Cells, T-Lymphocytes, Receptors, Immunologic, Tumor Microenvironment, Antigens, CD

Comments

PMID: 38113030