Emerging immune checkpoints in the post-PD-1 era: mechanisms and therapeutic applications

18.6K
views
46
authors
4
articles
Editors
2
Impact
Loading...
Original Research
21 September 2022
Blocking LAIR1 signaling in immune cells inhibits tumor development
Jingjing Xie
18 more and 
Cheng Cheng Zhang

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.

8,876 views
15 citations
Open for submission
Recommended Research Topics
Frontiers Logo

Frontiers in Immunology

Calcium Signaling in Cancer Immunity
Edited by Consuelo Amantini, Maria Beatrice Morelli
14.7K
views
38
authors
5
articles
Frontiers Logo

Frontiers in Immunology

The Therapeutic Inhibition of Macrophage Checkpoints
Edited by Alexandre P.A. Theocharides, Yasuyuki Saito, Gregor Hutter
33.5K
views
66
authors
6
articles
Frontiers Logo

Frontiers in Immunology

Spatial Immune Cell Heterogeneity in the Tumor Microenvironment
Edited by Joe Yeong, Sumit Mukherjee, Sheila Spada, Dr Anirban Ganguly
28.9K
views
46
authors
5
articles
Frontiers Logo

Frontiers in Immunology

Beyond PD-1: novel checkpoint receptors and ligands as targets for immunotherapy
Edited by Jesse Haramati, Dallas Flies
Deadline
01 Jun 2024
Submit
Frontiers Logo

Frontiers in Immunology

Predictive Biomarkers of Immunotherapy Response in Sarcomas
Edited by Lorenzo D'Ambrosio, Noel De Miranda
Deadline
31 Jan 2024
Submit