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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Brahmer, J., Reckamp, K. L., Baas, P., Crinò, L., Eberhardt, W. E. E., Poddubskaya, E., Antonia, S., Pluzanski, A., Vokes, E. E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504627 · Cited by 8,447
Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., Evdemon-Hogan, M., Conejo-Garcia, J. R., Zhang, L., Burow, M., et al. (2004) · Nature Medicine · doi:10.1038/nm1093 · Cited by 5,151
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
Zou, W., Wolchok, J. D., & Chen, L. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad7118 · Cited by 2,400
Suppression of inflammation by a synthetic histone mimic
Nicodeme, E., Jeffrey, K. L., Schaefer, U., Beinke, S., Dewell, S., Chung, C.-W., Chandwani, R., Marazzi, I., Wilson, P., Coste, H., et al. (2010) · Nature · doi:10.1038/nature09589 · Cited by 1,563
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
Mahoney, K. M., Rennert, P. D., & Freeman, G. J. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4591 · Cited by 1,294
Targeting bromodomains: epigenetic readers of lysine acetylation
Filippakopoulos, P., & Knapp, S. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4286 · Cited by 1,243
Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers
Bitler, B. G., Aird, K. M., Garipov, A., Li, H., Amatangelo, M., Kossenkov, A. V., Schultz, D. C., Liu, Q., Shih, I.-M., Conejo-Garcia, J. R., et al. (2015) · Nature Medicine · doi:10.1038/nm.3799 · Cited by 678
Self-citationEvolving synergistic combinations of targeted immunotherapies to combat cancer
Melero, I., Berman, D. M., Aznar, M. A., Korman, A. J., Gracia, J. L. P., & Haanen, J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3973 · Cited by 637
Big opportunities for small molecules in immuno-oncology
Adams, J. L., Smothers, J., Srinivasan, R., & Hoos, A. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4596 · Cited by 471
Conejo-Garcia, J. R., Benencia, F., Courreges, M.-C., Kang, E., Mohamed-Hadley, A., Buckanovich, R. J., Holtz, D. O., Jenkins, A., Na, H., Zhang, L., et al. (2004) · Nature Medicine · doi:10.1038/nm1097 · Cited by 437
Self-citationBelkina, A. C., Nikolajczyk, B. S., & Denis, G. V. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202838 · Cited by 418
Alterations of immune response of non-small cell lung cancer with Azacytidine
Wrangle, J., Wang, W., Koch, A., Easwaran, H., Mohammad, H. P., Pan, X., Vendetti, F., VanCriekinge, W., DeMeyer, T., Du, Z., et al. (2013) · Oncotarget · doi:10.18632/oncotarget.1542 · Cited by 386
Webb, J. R., Milne, K., Kroeger, D. R., & Nelson, B. H. (2016) · Gynecologic Oncology · doi:10.1016/j.ygyno.2016.03.008 · Cited by 335
Ovarian cancer progression is controlled by phenotypic changes in dendritic cells
Scarlett, U. K., Rutkowski, M. R., Rauwerdink, A. M., Fields, J., Escovar-Fadul, X., Baird, J., Cubillos-Ruiz, J. R., Jacobs, A. C., Gonzalez, J. L., Weaver, J., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20111413 · Cited by 315
Self-citationMok, S. C., Bonome, T., Vathipadiekal, V., Bell, A., Johnson, M. E., Wong, K.-K., Park, D.-C., Hao, K., Yip, D. K. P., Donninger, H., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.10.018 · Cited by 255
Abiko, K., Mandai, M., Hamanishi, J., Yoshioka, Y., Matsumura, N., Baba, T., Yamaguchi, K., Murakami, R., Yamamoto, A., Kharma, B., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2199 · Cited by 221
Cubillos-Ruiz, J. R., Engle, X., Scarlett, U. K., Martinez, D., Barber, A., Elgueta, R., Wang, Nesbeth, Y., Durant, Gewirtz, A. T., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37716 · Cited by 208
Self-citationBaratta, M. G., Schinzel, A. C., Zwang, Y., Bandopadhayay, P., Bowman-Colin, C., Kutt, J., Curtis, J., Piao, H., Wong, L. C., Kung, A. L., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1422165112 · Cited by 168
Self-citationGoundiam, O., Gestraud, P., Popova, T. G., Rouge, T. D. L. M., Fourchotte, V., Gentien, D., Hupé, P., Becette, V., Houdayer, C., Roman‐Roman, S., et al. (2015) · International Journal of Cancer · doi:10.1002/ijc.29568 · Cited by 64
Nesbeth, Y. C., Scarlett, U. K., Cubillos‐Ruiz, J. R., Martinez, D. G., Engle, X. A., Turk, M.-J., & Conejo-Garcia, J. R. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4329 · Cited by 61
Self-citation
Cited by
Mechanisms Controlling PD-L1 Expression in Cancer
Cha, J.-H., Chan, L.-C., Li, C.-W., Hsu, J. L., & Hung, M.-C. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.030 · Cited by 1,045
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).”
BackgroundA cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors
Wang, T., Wang, D., Yu, H., Feng, B., Zhou, F., Zhang, H., Zhou, L., Jiao, S., & Li, Y. (2018) · Nature Communications · doi:10.1038/s41467-018-03915-4 · Cited by 391
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)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
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.
