Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4
Abstract
Interaction of the B7 molecule on antigen-presenting cells with its receptors CD28 and CTLA-4 on T cells provides costimulatory signals for T cell activation. We have studied the effects of B7 on antitumor immunity to a murine melanoma that expresses a rejection antigen associated with the E7 gene product of human papillomavirus 16. While this E7+ tumor grows progressively in immunocompetent hosts, cotransfection of its cells with B7 led to tumor regression by a B7-dependent immune response mediated by CD8+ cytolytic T lymphocytes. The immune response induced by E7+B7+ tumor cells also caused regression of E7+B7- tumors at distant sites and was curative for established E7+B7- micrometastases. Our findings suggest that increasing T cell costimulation through the CD28 and CTLA-4 receptors may have therapeutic usefulness for generating immunity against tumors expressing viral antigens.
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In animal models, introducing B7-1 into tumors or blocking inhibitory B7 family members reduces tumor growth or causes spontaneous tumor rejection.
“Animal model studies have shown that introduction of B7-1 into tumors by transfection or blockade of inhibitory B7 family members can reduce tumor growth or result in spontaneous tumor rejection in vivo [7–13].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [11]
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- Authors
- Chen, L., Ashe, S., Brady, W. A., Hellström, I., Hellström, K. E., Ledbetter, J. A., McGowan, P., & Linsley, P. S.
- Affiliations
- Bristol-Myers Squibb (United States) (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1992-12
- Volume
- 71
- Issue
- 7
- Pages
- 1093-1102
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1978416272
- Cited by
- 1,050
- References
- 52
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 10 · 2023: 10 · 2022: 7 · 2021: 2 · 2020: 15 · 2019: 18 · 2018: 13 · 2017: 12 · 2016: 5 · 2015: 17 · 2014: 9 · 2013: 13 · 2012: 8
- FWCI
- 30.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- B7 costimulation, CD28, CTLA-4, T cell costimulation, antitumor immunity, murine melanoma, tumor regression, micrometastases, antigen-presenting cells
- MeSH terms
- Abatacept, Animals, Antigens, Differentiation, Antigens, Differentiation, T-Lymphocyte, Antigens, Surface, Antigens, Viral, Cell Line, Female, Lymphocyte Activation, Mice, Inbred C3H, Neoplasm Regression, Spontaneous, Neoplasms, Experimental, T-Lymphocytes, Cytotoxic, Transfection, Antigens, CD, CD28 Antigens, Immunoconjugates, Mice, CTLA-4 Antigen
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