Blocking LAIR1 signaling in immune cells inhibits tumor development
Open accessAbstract
The current immune checkpoint blockade therapy has been successful in treating some cancers but not others. New molecular targets and therapeutic approaches of cancer immunology need to be identified. Leukocyte associated immunoglobulin like receptor 1 (LAIR1) is an immune inhibitory receptor expressing on most immune cell types. However, it remains a question whether we can specifically and actively block LAIR1 signaling to activate immune responses for cancer treatment. Here we report the development of specific antagonistic anti-LAIR1 monoclonal antibodies and studied the effects of LAIR1 blockade on the anti-tumor immune functions. The anti-LAIR1 antagonistic antibody stimulated the activities of T cells, natural killer cells, macrophages, and dendritic cells in vitro. The single-cell RNA sequencing analysis of intratumoral immune cells in syngeneic human LAIR1 transgenic mice treated with control or anti-LAIR1 antagonist antibodies indicates that LAIR1 signaling blockade increased the numbers of CD4 memory T cells and inflammatory macrophages, but decreased those of pro-tumor macrophages, regulatory T cells, and plasmacytoid dendritic cells. Importantly, the LAIR1 blockade by the antagonistic antibody inhibited the activity of immunosuppressive myeloid cells and reactivated T cells from cancer patients in vitro and impeded tumor metastasis in a humanized mouse model. Blocking LAIR1 signaling in immune cells represents a promising strategy for development of anti-cancer immunotherapy.
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Patient-derived MDSCs suppressed the proliferation and function of autologous T cells in a coculture system.
“As expected, patient-derived MDSCs suppressed the proliferation and function of autologous T cells in a coculture system (Fig. 3c–e and Supplementary Fig. 5b), which is consistent with their known immunosuppressive activity31,32.”
From Oligomeric cystatin C supports the immunosuppressive activity of myeloid cells through interaction with inhibitory receptors (2025) · cites this paper as [31]
The Results section ('LAIR1 inhibition restored T cell proliferation in coculture'; page unavailable) reports that patient-derived MDSCs inhibited autologous T-cell proliferation and describes this as immunosuppressive activity. It does not report a separate measure of T-cell function in that coculture, so the additional claim about suppressed function is not independently supported. (LLM, conf=0.86)
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- Authors
- Xie, J., Gui, X., Deng, M., Chen, H., Chen, Y., Liu, X., Ku, Z., Tan, L., Huang, R., He, Y., Zhang, B., Lewis, C., Chen, K., Xu, L., Xu, J., Huang, T., Liao, X. C., Zhang, N., An, Z., & Zhang, C. C.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- The University of Texas Health Science Center at Houston (US)
- Harold C. Simmons Comprehensive Cancer Center (US)
- Children's Medical Center (US)
- Corresponding author
- An, Zhiqiang
- Zhang, Cheng Cheng
- ORCID
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2022-09-21
- Volume
- 13
- Pages
- 996026-996026
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC9534319
- OpenAlex
- W4296736496
- Cited by
- 36
- References
- 47
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 14 · 2023: 5
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (1R01 CA248736 , 5P30CA142543)
- U.S. Department of Defense
- Cancer Prevention and Research Institute of Texas
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- LAIR-1, immune checkpoint blockade, inhibitory receptors, tumor immunology, antitumor immunity, T cell activation, natural killer cells, macrophages, dendritic cells, regulatory T cells, memory CD4+ T cells, metastasis, humanized mice, cancer immunotherapy
- MeSH terms
- Immune Checkpoint Inhibitors, Animals, Antibodies, Monoclonal, Humans, Immunotherapy, Neoplasms, T-Lymphocytes, Regulatory, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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