CTLA-4: new insights into its biological function and use in tumor immunotherapy

Egen, Jackson G.; Kuhns, Michael S.; Allison, James P.

doi:10.1038/ni0702-611

Cited by 940Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

CTLA-4: new insights into its biological function and use in tumor immunotherapy

Egen, Jackson G., Kuhns, Michael S., Allison, James P.·2002·Nature Immunology

DOI 10.1038/ni0702-611

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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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CTLA-4 participates in the negative regulation of T cell activation and proliferation, which suppresses anti-tumor response.
“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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Restoring function in exhausted CD8 T cells during chronic viral infection
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Tumor Microenvironment‐Activatable Prodrug Vesicles for Nanoenabled Cancer Chemoimmunotherapy Combining Immunogenic Cell Death Induction and CD47 Blockade
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Phase I/II Study of Ipilimumab for Patients With Metastatic Melanoma
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Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo
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Authors: Egen, J. G., Kuhns, M. S., & Allison, J. P.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Allison, James P.
ORCID: Egen, Jackson G.
Kuhns, Michael S.
Allison, James P.
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2002-07
Volume: 3
Issue: 7
Pages: 611-618
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni0702-611
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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CTLA-4: new insights into its biological function and use in tumor immunotherapy

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