The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Ibrutinib treatment improves T cell number and function in CLL patients
Open accessAbstract
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially. T cell phenotype, immune function, and CLL cell immunosuppressive capacity were evaluated. RESULTS: Ibrutinib markedly increased CD4+ and CD8+ T cell numbers in CLL patients. This effect was more prominent in effector/effector memory subsets and was not observed with acalabrutinib. Ex vivo studies demonstrated that this may be due to diminished activation-induced cell death through ITK inhibition. PD-1 and CTLA-4 expression was significantly markedly reduced in T cells by both agents. While the number of Treg cells remained unchanged, the ratio of these to conventional CD4+ T cells was reduced with ibrutinib, but not acalabrutinib. Both agents reduced expression of the immunosuppressive molecules CD200 and BTLA as well as IL-10 production by CLL cells. CONCLUSIONS: Ibrutinib treatment increased the in vivo persistence of activated T cells, decreased the Treg/CD4+ T cell ratio, and diminished the immune-suppressive properties of CLL cells through BTK-dependent and -independent mechanisms. These features provide a strong rationale for combination immunotherapy approaches with ibrutinib in CLL and other cancers. TRIAL REGISTRATION: ClinicalTrials.gov NCT01589302 and NCT02029443. Samples described here were collected per OSU-0025. FUNDING: The National Cancer Institute.
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Cited by
Role of Bruton’s tyrosine kinase in B cells and malignancies
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Kinase inhibition in autoimmunity and inflammation
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Targeting B cell receptor signalling in cancer: preclinical and clinical advances
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Metadata
- Authors
- Long, M., Beckwith, K., Do, P., Mundy, B. L., Gordon, A., Lehman, A. M., Maddocks, K. J., Cheney, C., Jones, J. A., Flynn, J. M., Andritsos, L. A., Awan, F., Fraietta, J. A., June, C. H., Maus, M. V., Woyach, J. A., Caligiuri, M. A., Johnson, A. J., Muthusamy, N., & Byrd, J. C.
- Venue
- Journal of Clinical Investigation
- Published
- 2017-07-17
- Volume
- 127
- Issue
- 8
- Pages
- 3052-3064
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2734526350
- Cited by
- 388
- References
- 54
- FWCI
- 17.13
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Long, M., Beckwith, K., Do, P., Mundy, B. L., Gordon, A., Lehman, A. M., Maddocks, K. J., Cheney, C., Jones, J. A., Flynn, J. M., Andritsos, L. A., Awan, F., Fraietta, J. A., June, C. H., Maus, M. V., Woyach, J. A., Caligiuri, M. A., Johnson, A. J., Muthusamy, N., & Byrd, J. C. (2017). Ibrutinib treatment improves T cell number and function in CLL patients. Journal of Clinical Investigation. https://doi.org/10.1172/jci89756
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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.
