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Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function
Open accessAbstract
The interaction between tumor and the immune system is still poorly understood. Significant clinical responses have been achieved in cancer patients treated with antibodies against the CTLA4 and PD-1/PD-L1 checkpoints; however, only a small portion of patients responded to the therapies, indicating a need to explore additional co-inhibitory molecules for cancer treatment. B7-H3, a member of the B7 superfamily, was previously shown by us to inhibit T-cell activation and autoimmunity. In this study, we have analyzed the function of B7-H3 in tumor immunity. Expression of B7-H3 was found in multiple tumor lines, tumor-infiltrating dendritic cells, and macrophages. B7-H3-deficient mice or mice treated with an antagonistic antibody to B7-H3 showed reduced growth of multiple tumors, which depended on NK and CD8+ T cells. With a putative receptor expressed by cytotoxic lymphocytes, B7-H3 inhibited their activation, and its deficiency resulted in increased cytotoxic lymphocyte function in tumor-bearing mice. Combining blockades of B7-H3 and PD-1 resulted in further enhanced therapeutic control of late-stage tumors. Taken together, our results indicate that the B7-H3 checkpoint may serve as a novel target for immunotherapy against cancer.
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“B7H3 has been shown to promote tumor metastasis and invasion via suppression of both CD8+ and CD4 + T cell proliferation and activity86,87.”
From The evolving landscape of antibody-drug conjugates (ADCs) for treatment of prostate cancer (2025) · cites this paper as [86]
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Metadata
- Authors
- Lee, Y.-H., Martin-Orozco, N., Zheng, P., Li, J., Zhang, P., Tan, H., Park, H. J., Jeong, M., Chang, S. H., Kim, B.-S., Xiong, W., Zang, W., Guo, L., Liu, Y., Dong, Z.-J., Overwijk, W. W., Hwu, P., Yi, Q., Kwak, L., Yang, Z., Mak, T. W., Li, W., Radvanyi, L. G., Ni, L., Liu, D., & Dong, C.
- Affiliations
- Houston Methodist (US)
- Tsinghua University (CN)
- Children's National (US)
- China-Japan Friendship Hospital (CN)
- Baylor College of Medicine (US)
- Central South University (CN)
- Cleveland Clinic (US)
- City Of Hope National Medical Center (US)
- University Health Network (CA)
- EMD Serono, Inc. (United States) (US)
- Corresponding author
- Dong, Chen
- ORCID
- Venue
- Cell Research
- Published
- 2017-07-07
- Volume
- 27
- Issue
- 8
- Pages
- 1034-1045
- ISSN
- 1001-0602 (ISSN-L)
- 1748-7838
- PMC
- PMC5539354
- OpenAlex
- W2725962181
- Cited by
- 328
- References
- 32
- Citations by year
- 2026: 20 · 2025: 36 · 2024: 33 · 2023: 44 · 2022: 60 · 2021: 49 · 2020: 43 · 2019: 24 · 2018: 14 · 2017: 5
- FWCI
- 10.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- National Natural Science Foundation of China (81502462)
- Tsinghua University
- EMD Serono
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- B7-H3, immune checkpoint, tumor immunology, cytotoxic lymphocytes, natural killer cells, CD8+ T cells, tumor-infiltrating dendritic cells, tumor-associated macrophages, anti-PD-1 therapy, cancer immunotherapy, tumor growth inhibition
- MeSH terms
- Animals, Female, Humans, Immunity, Cellular, Killer Cells, Natural, Male, Mice, Inbred BALB C, Neoplasm Proteins, Neoplasms, Mice, Knockout, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Mice, B7 Antigens
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