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Cited by 24Cancer Immunotherapy and BiomarkersImmune cells in cancerGalectins and Cancer Biology

LILRB3 Supports Immunosuppressive Activity of Myeloid Cells and Tumor Development

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Huang, Ryan, Liu, Xiaoye, Kim, Jaehyup, Deng, Hui, Deng, Mi, Gui, Xun, Chen, Heyu, Wu, Guojin +13 more·2024·Cancer Immunology Research
DOI 10.1158/2326-6066.cir-23-0496PMC PMC10932818

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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.

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Authors
Huang, R., Liu, X., Kim, J., Deng, H., Deng, M., Gui, X., Chen, H., Wu, G., Xiong, W., Xie, J., Lewis, C., Homsi, J., Yang, X., Zhang, C., He, Y., Lou, Q., Smith, C., John, S., Zhang, N., An, Z., & Zhang, C. C.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
  • Harold C. Simmons Comprehensive Cancer Center (US)
  • 1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas.
ORCID
Venue
Cancer Immunology Research
Publisher
American Association for Cancer Research (AACR)
Published
2023-12-19
Volume
12
Issue
3
Pages
350-362
ISSN
  • 2326-6066 (ISSN-L)
  • 2326-6074
DOI
10.1158/2326-6066.cir-23-0496
PMC
PMC10932818
OpenAlex
W4389935829
Cited by
24
References
2
Citations by year
2026: 7 · 2025: 9 · 2024: 8
FWCI
2.93
Type
journal article
Language
en
Open access
Locations
  • Cancer Immunology Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
Funders
  • National Cancer Institute (R01CA248736, R01CA263079, 5P30CA142543, Lung Cancer SPORE Development Research Program at UT Southwestern)
  • Cancer Prevention and Research Institute of Texas (RP220032, RP15150551, RP190561)
  • Welch Foundation (AU-0042-20030616)
  • Leukemia and Lymphoma Society (6629-21)
  • Immune-Onc Therapeutics, Inc. (Sponsored Research Grant #111077)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Galectins and Cancer Biology
Keywords
LILRB3, immunosuppressive myeloid cells, myeloid-derived suppressor cells, galectin-4, galectin-7, immune checkpoint blockade, carcinogenesis, solid tumors, T cell-dependent immunity, cancer immunotherapy
MeSH terms
Myeloid-Derived Suppressor Cells, Animals, Humans, Neoplasms, Receptors, Immunologic, T-Lymphocytes, Antigens, CD, Myeloid Cells, Mice, Tumor Microenvironment

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