The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
The Mechanism of Anti-CTLA-4 Activity and the Negative Regulation of T-Cell Activation
Open accessAbstract
The survival rate of patients diagnosed with late-stage melanoma is poor—only 5%–10%. Enlisting the immune system in the fight against cancers such as melanoma could help improve the prognosis of these patients. Data have shown that melanocyte proteins make good targets for immune system–based therapy in this disease. However, self-tolerance, which develops to inhibit autoimmune attack, makes this strategy difficult. Two proteins on the surface of T cells—CD28 and cytotoxic T-lymphocyte antigen 4 (CTLA-4)—play important roles in the regulation of immune activation and tolerance. CD28 provides positive modulatory signals in the early stages of an immune response, while CTLA-4 signaling inhibits T-cell activation, particularly during strong T-cell responses. CTLA-4 blockade using anti—CTLA-4 monoclonal antibody therapy has great appeal because suppression of inhibitory signals results in the generation of an antitumor T-cell response. Both clinical and preclinical data indicate that CTLA-4 blockade results in direct activation of CD4+ and CD8+ effector cells, and anti–CTLA-4 monoclonal antibody therapy has shown promise in a number of cancers, particularly melanoma. Interestingly, the occurrence of adverse events among patients treated with CTLA-4 blockade helps shed light on the mechanism of action of anti–CTLA-4 monoclonal antibodies. Most adverse events involve immune-related toxicity to the skin and gastrointestinal tract. Major gastrointestinal toxicity develops in up to 21% of treated patients, and while an objective response occurs in approximately 36% of melanoma patients who develop enterocolitis with treatment, an objective response is found in only 11% of patients who do not experience this adverse reaction.
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Cites
CD28/B7 SYSTEM OF T CELL COSTIMULATION
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CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
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“Furthermore, other preclinical studies have demonstrated that, whereas blockade of CD28 inhibits antitumor immunity, blockade of CTLA-4 stimulates antitumor immunity [ 13 , 23].”
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“Preclinical studies also have shown antitumor efficacy for anti–CTLA-4 monoclonal antibody therapy in conjunction with vaccines [3, 46 ].”
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CTLA-4: new insights into its biological function and use in tumor immunotherapy
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“tial enhancement of effector T-cell activity secondary to reduction in regulation [ 17 ].”
Background
Cited by
Wolchok, J. D., Hoos, A., O'Day, S., Weber, J. S., Hamid, O., Lebbé, C., Maio, M., Binder, M., Bohnsack, O., Nichol, G., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1624 · Cited by 3,222
Self-citationTherapeutic developments in pancreatic cancer: current and future perspectives
Neoptolemos, J. P., Kleeff, J., Michl, P., Costello, E., Greenhalf, W., & Palmer, D. H. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0005-x · Cited by 1,170
Rodig, S. J., Gusenleitner, D., Jackson, D. G., Gjini, E., Giobbie-Hurder, A., Jin, C., Chang, H., Lovitch, S. B., Horak, C., Weber, J. S., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aar3342 · Cited by 579
Self-citationResistance to PD1/PDL1 checkpoint inhibition
O'Donnell, J. S., Long, G. V., Scolyer, R. A., Teng, M. W. L., & Smyth, M. J. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.11.007 · Cited by 572
Myeloid-Derived Suppressor Cells Hinder the Anti-Cancer Activity of Immune Checkpoint Inhibitors
Weber, R., Fleming, V., Hu, X., Nagibin, V., Groth, C., Altevogt, P., Utikal, J., & Umansky, V. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01310 · Cited by 538
Metadata
- Authors
- Wolchok, J. D., & Saenger, Y.
- Venue
- The Oncologist
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-10-01
- Volume
- 13
- Issue
- S4
- Pages
- 2-9
- ISSN
- 1083-7159 (ISSN-L)
- 1549-490X
- OpenAlex
- W2144952279
- Cited by
- 250
- References
- 11
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Wolchok, J. D., & Saenger, Y. (2008). The Mechanism of Anti-CTLA-4 Activity and the Negative Regulation of T-Cell Activation. The Oncologist. https://doi.org/10.1634/theoncologist.13-s4-2
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
