Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Supplemental material
  • Version history
  • Article usage
  • Citations to this article

Advertisement

ResearchIn-Press PreviewOncology Open Access | 10.1172/JCI184043

Blocking immune checkpoint LAIR1 with antibody blockade or 3-in-1 CAR T cells enhances antitumor response

Haipeng Tao,1 Dongjiang Chen,1 Changlin Yang,1 Duy T. Nguyen,2 Georges Abboud,1 Ruixuan Liu,1 Tianyi Liu,1 Avirup Chakraborty,1 Alicia Y. Hou,1 Nicole A. Petit,1 Muhammad Abbas,1 Robert W. Davis,1 Janie Zhang,1 Christina Von Roemeling,1 Mohammed O. Gbadamosi,1 Linchun Jin,1 Tongjun Gu,3 Tuo Lin,4 Pengchen Wang,4 Alfonso Pepe,2 Diego Ivan Pedro,2 Hector R. Mendez-Gomez,1 Chao Xie,1 Aida Karachi,1 Frances Weidert,1 Dan Jin,1 Chenggang Wang,1 Kaytora Long-James,1 Elizabeth K. Molchan,1 Paul Castillo,7 John A. Ligon,7 Ashley P. Ghiaseddin,1 Elias J. Sayour,1 Maryam Rahman,1 Loic P. Deleyrolle,1 Betty Y.S. Kim,8 Duane A. Mitchell,1 W. Gregory Sawyer,2 and Jianping Huang1

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Tao, H. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Chen, D. in: PubMed | Google Scholar |

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Yang, C. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Nguyen, D. in: PubMed | Google Scholar |

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Abboud, G. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Liu, R. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Liu, T. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Chakraborty, A. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Hou, A. in: PubMed | Google Scholar |

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Petit, N. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Abbas, M. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Davis, R. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Zhang, J. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Von Roemeling, C. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Gbadamosi, M. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Jin, L. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Gu, T. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Lin, T. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Wang, P. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Pepe, A. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Pedro, D. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Mendez-Gomez, H. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Xie, C. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Karachi, A. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Weidert, F. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Jin, D. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Wang, C. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Long-James, K. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Molchan, E. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Castillo, P. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Ligon, J. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Ghiaseddin, A. in: PubMed | Google Scholar |

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Sayour, E. in: PubMed | Google Scholar |

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Rahman, M. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Deleyrolle, L. in: PubMed | Google Scholar |

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Kim, B. in: PubMed | Google Scholar |

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Mitchell, D. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Sawyer, W. in: PubMed | Google Scholar

1Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, United States of America

2The Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, United States of America

3Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States of America

4Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, United States of America

5Division of Quantitative Sciences, Department of Biostatistics, University of Florida Health Cancer Center, University of Florida, Gainesville, China

6Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, China

7Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Florida, Gainesville, United States of America

8Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, United States of America

Find articles by Huang, J. in: PubMed | Google Scholar

Published July 1, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI184043.
Copyright © 2025, Tao et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published July 1, 2025 - Version history
View PDF
Abstract

Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment (TME) and dampen the immune response, negatively affecting patient survival. Therefore, targeting TAMs could address the limitations of current cancer treatments. However, drug development in this area remains limited. The Leukocyte-associated Immunoglobulin-like Receptor-1 (LAIR1), also called CD305, is prominently expressed on the surface of TAMs. We have uncovered a previously unrecognized immunosuppressive LAIR1 → Factor XIII A (FXIII-A) → Collagen IV pathway across various cancer types. Inhibition of LAIR1, either through knockout (Lair1–/–), antibody blockade (aLAIR1), or a chimeric antigen receptor (CAR) design (3-in-1 CAR by combining tumor targeting, T cell trafficking, and remodeling of the immunosuppressive TME in one CAR construct) provides enhanced antitumor response. LAIR1 inhibition enhances peripheral and intratumoral CD8 memory T-cell populations, induces a phenotypic shift of M2-like Macrophages towards M1, and normalizes tumor collagen IV and structural components in the TME, facilitating effective tumor-T cell interactions and tumor suppression. Enhanced antitumor responses were observed when Lair1–/– or aLAIR1 was used alone or combined with CAR T cells or when the 3-in-1 CAR T cells were used solely in chemotherapy-radiation-PD-1 blockade-resistant tumor models. These findings position LAIR1 inhibition as a promising strategy for cancer immunotherapies.

Graphical Abstract
graphical abstract
Supplemental material

View

View Video 1A 8R-70CAR T + M2-like Macrophage+Tumor+aLAIR1

View Video 1B 8R-70CAR T + M2-like Macrophage + Tumor + IgG

View Video 1C NAS T + M2-like Macrophage+ Tumor + aLAIR1

View Video 1D NAS T + M2-like Macrophage + Tumor + IgG

View Unedited blot and gel images

View Confirmation of Publication and Licensing Rights

Version history
  • Version 1 (July 1, 2025): In-Press Preview

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Supplemental material
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts