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CTLA-4: new insights into its biological function and use in tumor immunotherapy
Abstract
The discovery of multiple costimulatory cell surface molecules that influence the course of T cell activation has increased our appreciation of the complexity of the T cell response. It remains clear, however, that CD28 and cytotoxic T lymphocyte antigen 4 (CTLA-4) are the critical costimulatory receptors that determine the early outcome of stimulation through the T cell antigen receptor (TCR). Details of how the T cell integrates TCR stimulation with the costimulatory signals of CD28 and the inhibitory signals of CTLA-4 remain to be established, but unique features of the cell biology of CTLA-4 provide important insights into its function. We summarize here recent findings that suggest a previously unrecognized role for CTLA-4 in the regulation of T cell responses. We also describe preclinical and clinical results that indicate manipulation of CTLA-4 has considerable promise as a strategy for the immunotherapy of cancer.
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“Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) participates in the negative regulation of T cell activation and proliferation, which suppresses anti-tumor response [91].”
From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [91]
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Metadata
- Authors
- Egen, J. G., Kuhns, M. S., & Allison, J. P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Allison, James P.
- Venue
- Nature Immunology
- Published
- 2002-07
- Volume
- 3
- Issue
- 7
- Pages
- 611-618
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2140460887
- Cited by
- 940
- References
- 93
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 30 · 2023: 34 · 2022: 45 · 2021: 50 · 2020: 43 · 2019: 33 · 2018: 27 · 2017: 36 · 2016: 28 · 2015: 32 · 2014: 31 · 2013: 38 · 2012: 25
- FWCI
- 5.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Cancer Institute (CA40041, R01CA057986, CA57986)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CTLA-4, costimulatory receptors, CD28, T cell activation, T cell receptor signaling, T cell regulation, cancer immunotherapy, CTLA-4 blockade, immune checkpoint blockade
- MeSH terms
- Abatacept, Animals, Antigens, Differentiation, Cell Division, Colonic Neoplasms, Disease Models, Animal, Fibrosarcoma, Gene Expression Regulation, Humans, Immunotherapy, Lymphocyte Activation, Neoplasms, T-Lymphocytes, Antigens, CD, Immunoconjugates, Mice, CTLA-4 Antigen
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