Blocking LAIR1 signaling in immune cells inhibits tumor development
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 expres...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.996026/full |
| _version_ | 1811183723834507264 |
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| author | Jingjing Xie Xun Gui Mi Deng Heyu Chen Yuanzhi Chen Xiaoye Liu Zhiqiang Ku Lingxiao Tan Ryan Huang Yubo He Bruce Zhang Cheryl Lewis Kenian Chen Kenian Chen Lin Xu Lin Xu Jian Xu Tao Huang X. Charlene Liao Ningyan Zhang Zhiqiang An Cheng Cheng Zhang |
| author_facet | Jingjing Xie Xun Gui Mi Deng Heyu Chen Yuanzhi Chen Xiaoye Liu Zhiqiang Ku Lingxiao Tan Ryan Huang Yubo He Bruce Zhang Cheryl Lewis Kenian Chen Kenian Chen Lin Xu Lin Xu Jian Xu Tao Huang X. Charlene Liao Ningyan Zhang Zhiqiang An Cheng Cheng Zhang |
| author_sort | Jingjing Xie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:51:48Z |
| format | Article |
| id | doaj.art-6d65a3dbcada490eaa67ace0038064dd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T09:51:48Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6d65a3dbcada490eaa67ace0038064dd2022-12-22T04:30:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.996026996026Blocking LAIR1 signaling in immune cells inhibits tumor developmentJingjing Xie0Xun Gui1Mi Deng2Heyu Chen3Yuanzhi Chen4Xiaoye Liu5Zhiqiang Ku6Lingxiao Tan7Ryan Huang8Yubo He9Bruce Zhang10Cheryl Lewis11Kenian Chen12Kenian Chen13Lin Xu14Lin Xu15Jian Xu16Tao Huang17X. Charlene Liao18Ningyan Zhang19Zhiqiang An20Cheng Cheng Zhang21Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, United StatesDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, United StatesDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, United StatesTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, United StatesDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesHarold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United StatesChildren’s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, United StatesImmune-Onc Therapeutics, Inc, Palo Alto, CA, United StatesImmune-Onc Therapeutics, Inc, Palo Alto, CA, United StatesTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, United StatesTexas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, United StatesDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.996026/fullantibodycancer immunotherapyRNAseqT cellmyeloid cellsnatural killer cell |
| spellingShingle | Jingjing Xie Xun Gui Mi Deng Heyu Chen Yuanzhi Chen Xiaoye Liu Zhiqiang Ku Lingxiao Tan Ryan Huang Yubo He Bruce Zhang Cheryl Lewis Kenian Chen Kenian Chen Lin Xu Lin Xu Jian Xu Tao Huang X. Charlene Liao Ningyan Zhang Zhiqiang An Cheng Cheng Zhang Blocking LAIR1 signaling in immune cells inhibits tumor development Frontiers in Immunology antibody cancer immunotherapy RNAseq T cell myeloid cells natural killer cell |
| title | Blocking LAIR1 signaling in immune cells inhibits tumor development |
| title_full | Blocking LAIR1 signaling in immune cells inhibits tumor development |
| title_fullStr | Blocking LAIR1 signaling in immune cells inhibits tumor development |
| title_full_unstemmed | Blocking LAIR1 signaling in immune cells inhibits tumor development |
| title_short | Blocking LAIR1 signaling in immune cells inhibits tumor development |
| title_sort | blocking lair1 signaling in immune cells inhibits tumor development |
| topic | antibody cancer immunotherapy RNAseq T cell myeloid cells natural killer cell |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.996026/full |
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