The DOI matches its Crossref record; 93 of the 93 references it cites were found in a registry or an index.
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]
Citations
Cites
Enhancement of Antitumor Immunity by CTLA-4 Blockade
Leach, D. R., Krummel, M. F., & Allison, J. P. (1996) · Science · doi:10.1126/science.271.5256.1734 · Cited by 3,955
Self-citationTivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A., & Sharpe, A. H. (1995) · Immunity · doi:10.1016/1074-7613(95)90125-6 · Cited by 2,914
Dranoff, G., Jaffee, E. M., Lazenby, A., Golumbek, P. T., Levitsky, H., Brose, K., Jackson, V., Hamada, H., Pardoll, D. M., & Mulligan, R. C. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3539 · Cited by 2,820
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., Thompson, C. B., Griesser, H., & Mak, T. W. (1995) · Science · doi:10.1126/science.270.5238.985 · Cited by 2,766
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
Krummel, M. F., & Allison, J. P. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.2.459 · Cited by 2,245
Self-citationTakahashi, T., Tagami, T., Yamazaki, S., Uede, T., Shimizu, J., Sakaguchi, N., Mak, T. W., & Sakaguchi, S. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.2.303 · Cited by 2,233
CTLA-4 can function as a negative regulator of T cell activation
Walunas, T. L., Lenschow, D. J., Bakker, C. Y., Linsley, P. S., Freeman, G. J., Green, J. M., Thompson, C. B., & Bluestone, J. A. (1994) · Immunity · doi:10.1016/1074-7613(94)90071-x · Cited by 2,222
Read, S., Malmström, V., & Powrie, F. M. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.2.295 · Cited by 2,206
Salomon, B. L., Lenschow, D. J., Rhee, L., Ashourian, N., Singh, B., Sharpe, A. H., & Bluestone, J. A. (2000) · Immunity · doi:10.1016/s1074-7613(00)80195-8 · Cited by 2,058
Sharpe, A. H., & Freeman, G. J. (2002) · Nature reviews. Immunology · doi:10.1038/nri727 · Cited by 1,759
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Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 4,057
Self-citationFundamental Mechanisms of Immune Checkpoint Blockade Therapy
Wei, S. C., Duffy, C. R., & Allison, J. P. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0367 · Cited by 3,088
Self-citationCTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition
Buchbinder, E. I., & Desai, A. (2016) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000239 · Cited by 2,360
“Proposed mechanisms for such inhibitory signals include direct inhibition at the TCR immune synapse, inhibition of CD28 or its signaling pathway, or increased mobility of T cells leading to decreased ability to interact with APCs.(9,12,13) CTLA-4 itself is subject to regulation, particularly by localization within the…”
BackgroundGreenwald, R. J., Freeman, G. J., & Sharpe, A. H. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115611 · Cited by 2,318
Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease
Ueda, H., Howson, J. M. M., Esposito, L., Heward, J., Snook, Chamberlain, G., Rainbow, D. B., Hunter, K. M. D., Smith, A. N., Di Genova, G., et al. (2003) · Nature · doi:10.1038/nature01621 · Cited by 2,175
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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