The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression
Open accessAbstract
Restoration of anti-tumor immunity by blocking PD-L1 signaling through the use of antibodies has proven to be beneficial in cancer therapy. Here, we show that BET bromodomain inhibition suppresses PD-L1 expression and limits tumor progression in ovarian cancer. CD274 (encoding PD-L1) is a direct target of BRD4-mediated gene transcription. In mouse models, treatment with the BET inhibitor JQ1 significantly reduced PD-L1 expression on tumor cells and tumor-associated dendritic cells and macrophages, which correlated with an increase in the activity of anti-tumor cytotoxic T cells. The BET inhibitor limited tumor progression in a cytotoxic T-cell-dependent manner. Together, these data demonstrate a small-molecule approach to block PD-L1 signaling. Given the fact that BET inhibitors have been proven to be safe with manageable reversible toxicity in clinical trials, our findings indicate that pharmacological BET inhibitors represent a treatment strategy for targeting PD-L1 expression.
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Cites
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay-Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,256
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer
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Self-citationSelective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262
Self-citationImmune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.001 · Cited by 4,229
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Suppression of inflammation by a synthetic histone mimic
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Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies
Naidoo, J., Page, D. B., Li, B. T., Connell, L. C., Schindler, K., Lacouture, M. E., Postow, M. A., & Wolchok, J. D. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv383 · Cited by 1,470
Combination cancer immunotherapy and new immunomodulatory targets
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Targeting bromodomains: epigenetic readers of lysine acetylation
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Cited by
Regulation of PD-L1 expression in the tumor microenvironment
Yi, M., Niu, M., Xu, L., Luo, S., & Wu, K. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-01027-5 · Cited by 681
Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy
Lu, Y., Chan, Y.-T., Tan, H.-Y., Li, S., Wang, N., & Feng, Y. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01197-3 · Cited by 499
T Cell Dysfunction and Exhaustion in Cancer
Zhang, Z., Liu, S., Zhang, B., Qiao, L., Zhang, Y., & Zhang, Y. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00017 · Cited by 385
“Meanwhile, treatment with JQ1-α specific inhibitor of the histone acetylation reader bromodomain-containing protein 4 (BRD4)results in decreased PD-L1 expression on tumor cells and macrophages, which is correlated with an increase in antitumor T cell activity (Zhu et al., 2016).”
BackgroundThe cancer epigenome: Concepts, challenges, and therapeutic opportunities
Dawson, M. A. (2017) · Science · doi:10.1126/science.aam7304 · Cited by 377
BET inhibitors: a novel epigenetic approach
Doroshow, D. B., Eder, J. P., & LoRusso, P. M. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx157 · Cited by 367
Metadata
- Authors
- Zhu, H., Bengsch, F., Svoronos, N., Rutkowski, M. R., Bitler, B. G., Allegrezza, M. J., Yokoyama, Y., Kossenkov, A. V., Bradner, J. E., Conejo-Garcia, J. R., & Zhang, R.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 16
- Issue
- 11
- Pages
- 2829-2837
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2520148131
- Cited by
- 432
- References
- 24
- FWCI
- 15.80
- Type
- journal article
- Language
- en
- Open access
- gold
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
- Funders
- NIH/National Cancer Institute (CA160331, CA163377, CA202919, K99CA194318)
- U.S. Department of Defense (OC140632P1, OC150446)
- Jayne Koskinas & Ted Giovanis Breast Cancer Research Consortium
- Cancer Center Support Grant (CA010815)
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- CoChat. (2026). Citation check: BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression. https://app.cochat.ai/papers/10.1016/j.celrep.2016.08.032
- The paper
- Zhu, H., Bengsch, F., Svoronos, N., Rutkowski, M. R., Bitler, B. G., Allegrezza, M. J., Yokoyama, Y., Kossenkov, A. V., Bradner, J. E., Conejo-Garcia, J. R., & Zhang, R. (2016). BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression. Cell Reports. https://doi.org/10.1016/j.celrep.2016.08.032
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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.
