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PD-L1 Expression in Triple-Negative Breast Cancer
Open accessAbstract
Early-phase trials targeting the T-cell inhibitory molecule programmed cell death ligand 1 (PD-L1) have shown clinical efficacy in cancer. This study was undertaken to determine whether PD-L1 is overexpressed in triple-negative breast cancer (TNBC) and to investigate the loss of PTEN as a mechanism of PD-L1 regulation. The Cancer Genome Atlas (TCGA) RNA sequencing data showed significantly greater expression of the PD-L1 gene in TNBC (n = 120) compared with non-TNBC (n = 716; P < 0.001). Breast tumor tissue microarrays were evaluated for PD-L1 expression, which was present in 19% (20 of 105) of TNBC specimens. PD-L1+ tumors had greater CD8+ T-cell infiltrate than PD-L1− tumors (688 cells/mm vs. 263 cells/mm; P < 0.0001). To determine the effect of PTEN loss on PD-L1 expression, stable cell lines were generated using PTEN short hairpin RNA (shRNA). PTEN knockdown led to significantly higher cell-surface PD-L1 expression and PD-L1 transcripts, suggesting transcriptional regulation. Moreover, phosphoinositide 3-kinase (PI3K) pathway inhibition using the AKT inhibitor MK-2206 or rapamycin resulted in decreased PD-L1 expression, further linking PTEN and PI3K signaling to PD-L1 regulation. Coculture experiments were performed to determine the functional effect of altered PD-L1 expression. Increased PD-L1 cell surface expression by tumor cells induced by PTEN loss led to decreased T-cell proliferation and increased apoptosis. PD-L1 is expressed in 20% of TNBCs, suggesting PD-L1 as a therapeutic target in TNBCs. Because PTEN loss is one mechanism regulating PD-L1 expression, agents targeting the PI3K pathway may increase the antitumor adaptive immune responses. Cancer Immunol Res; 2(4); 361–70. ©2014 AACR.
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Citations
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945
Self-citationTriple-negative breast cancer: clinical features and patterns of recurrence
Dent, R., Trudeau, M., Pritchard, K. I., Hanna, W. M., Kahn, H. K., Sawka, C. A., Lickley, L. A., Rawlinson, E., Sun, P., & Narod, S. A. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-3045 · Cited by 5,091
Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
Krummel, M. F., & Allison, J. P. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.2.459 · Cited by 2,245 · cited 3×
“T cells were stimulated with anti-CD3 and anti-CD28 antibodies.”
Spranger, S., Spaapen, R. M., Zha, Y., Williams, J., Meng, Y., Ha, T. T., & Gajewski, T. F. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006504 · Cited by 1,677
Hamanishi, J., Mandai, M., Iwasaki, M., Okazaki, T., Tanaka, Y., Yamaguchi, K., Higuchi, T., Yagi, H., Takakura, K., Minato, N., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611533104 · Cited by 1,378
Cited by
Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer
Schmid, P., Adams, S., Rugo, H. S., Schneeweiss, A., Barrios, C. H., Iwata, H., Diéras, V., Hegg, R., Im, S.-A., Shaw Wright, G., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1809615 · Cited by 4,350
Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease
Bianchini, G., Balko, J. M., Mayer, I. A., Sanders, M. E., & Gianni, L. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.66 · Cited by 3,079
PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer
Glaviano, A., Foo, A. S. C., Lam, H. Y., Yap, K. C. H., Jacot, W., Jones, R. H., Eng, H., Nair, M. G., Makvandi, P., Geoerger, B., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01827-6 · Cited by 2,138
Immunological effects of conventional chemotherapy and targeted anticancer agents
Galluzzi, L., Buqué, A., Kepp, O., Zitvogel, L., & Kroemer, G. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.10.012 · Cited by 1,530
Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
Nanda, R., Chow, L. Q. M., Dees, E. C., Berger, R., Gupta, S., Geva, R., Pusztai, L., Pathiraja, K., Aktan, G., Cheng, J. D., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.64.8931 · Cited by 1,477
Schmid, P., Rugo, H. S., Adams, S., Schneeweiss, A., Barrios, C. H., Iwata, H., Diéras, V., Henschel, V., Molinero, L., Chui, S. Y., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30689-8 · Cited by 1,216
Liquid biopsy and minimal residual disease - latest advances and implications for cure
Pantel, K., & Alix-Panabières, C. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0187-3 · Cited by 1,110
Adams, S., Schmid, P., Rugo, H. S., Winer, E. P., Loirat, D., Awada, A., Cescon, D. W., Iwata, H., Campone, M., Nanda, R., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdy517 · Cited by 807
Regulation of PD-L1: a novel role of pro-survival signalling in cancer.
Chen, J., Jiang, C. C., Jin, L., & Zhang, X. D. (2016) · Annals of Oncology · doi:10.1093/annonc/mdv615 · Cited by 767
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
Loi, S., Dushyanthen, S., Beavis, P. A., Salgado, R., Denkert, C., Savas, P., Combs, S., Rimm, D. L., Giltnane, J. M., Estrada, M. V., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1125 · Cited by 536
Liu, J., Fan, L., Yu, H., Zhang, J., He, Y., Feng, D., Wang, F., Li, X., Liu, Q., Li, Y., et al. (2019) · Hepatology · doi:10.1002/hep.30607 · Cited by 449
Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review
Costa, R. L. B., Han, H. S., & Gradishar, W. J. (2018) · Breast Cancer Research and Treatment · doi:10.1007/s10549-018-4697-y · Cited by 439
Schmid, P., Salgado, R., Park, Y. H., Muñoz-Couselo, E., Kim, S. B., Sohn, J., Im, S.-A., Foukakis, T., Kuemmel, S., Dent, R., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.01.072 · Cited by 413
Constantinidou, A., Alifieris, C., & Trafalis, D. T. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.09.008 · Cited by 342
Fournel, L., Wu, Z., Stadler, N., Damotte, D., Lococo, F., Boulle, G., Ségal-Bendirdjian, E., Bobbio, A., Icard, P., Trédaniel, J., et al. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.08.005 · Cited by 249
Hudson, K., Cross, N., Jordan-Mahy, N., & Leyland, R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.568931 · Cited by 243
Cell membrane coated-nanoparticles for cancer immunotherapy
Zeng, Y., Li, S., Zhang, S., Wang, L., Yuan, H., & Hu, F. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.02.023 · Cited by 238
Immunomodulation by targeted anticancer agents
Petroni, G., Buqué, A., Zitvogel, L., Kroemer, G., & Galluzzi, L. (2021) · Cancer Cell · doi:10.1016/j.ccell.2020.11.009 · Cited by 212
Yang, L., Li, A., Lei, Q., & Zhang, Y. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0804-8 · Cited by 215
Castagnoli, L., Cancila, V., Cordoba-Romero, S. L., Faraci, S., Talarico, G., Belmonte, B., Iorio, M. V., Milani, M., Volpari, T., Chiodoni, C., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0700-2 · Cited by 184
Sceneay, J., Goreczny, G. J., Wilson, K., Morrow, S., DeCristo, M. J., Ubellacker, J. M., Qin, Y., Laszewski, T., Stover, D. G., Barrera, V., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1454 · Cited by 156
Self-citationSasidharan Nair, V., Toor, S. M., Ali, B. R., & Elkord, E. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1471137 · Cited by 159
Ruvolo, P. P. (2016) · BBA Clinical · doi:10.1016/j.bbacli.2016.08.002 · Cited by 143
Hypoxia and the phenomenon of immune exclusion
Pietrobon, V., & Marincola, F. M. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-020-02667-4 · Cited by 119
Chang, X., Wu, Q., Wu, Y., Xi, X., Cao, J., Chu, H., Liu, Q., Li, Y., Wu, W., Fang, X., et al. (2022) · Nano Letters · doi:10.1021/acs.nanolett.2c03260 · Cited by 109
Self-citationSoundararajan, R., Fradette, J., Konen, J., Moulder, S., Zhang, X., Gibbons, D., Varadarajan, N., Wistuba, I., Tripathy, D., Bernatchez, C., et al. (2019) · Cancers · doi:10.3390/cancers11050714 · Cited by 103
Yin, T., Zhao, Z.-B., Guo, J., Wang, T., Yang, J.-B., Wang, C., Long, J., Ma, S., Huang, Q., Zhang, K., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-3397 · Cited by 92
Iwata, H., Inoue, K., Kaneko, K., Ito, Y., Tsugawa, K., Hasegawa, A., Nakagawa, S., Kuratomi, H., & Tamura, K. (2019) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyz135 · Cited by 46
Oba, T., Kajihara, R., Yokoi, T., Repasky, E. A., & Ito, F. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-0939 · Cited by 26
Yuan, Y., Kos, F. J., He, T.-F., Yin, H. H., Li, M., Hardwick, N., Zurcher, K., Schmolze, D., Lee, P., Pillai, R. K., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1363138 · Cited by 23
Yue, L., Geng, F., Jin, J., Li, W., Liu, B., Du, M., Gao, X., Lü, J., & Pan, X. (2024) · Biotechnology Journal · doi:10.1002/biot.202400428 · Cited by 14
Immunotherapeutic strategies in breast cancer: a clinical update
Zhang, J. Q., & Plitas, G. (2021) · Journal of Surgical Oncology · doi:10.1002/jso.26287 · Cited by 6
Yuan, Z., Liu, Z., Zhou, M., Wen, H., & Li, B. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2025.105111 · Cited by 6
Metadata
- Authors
- Mittendorf, E. A., Philips, A. V., Meric-Bernstam, F., Qiao, N., Wu, Y., Harrington, S., Su, X., Wang, Y., Gonzalez-Angulo, A. M., Akcakanat, A., Chawla, A., Curran, M., Hwu, P., Sharma, P., Litton, J. K., Molldrem, J. J., & Alatrash, G.
- Venue
- Cancer Immunology Research
- Published
- 2014-04-01
- Volume
- 2
- Issue
- 4
- Pages
- 361-370
- ISSN
- 2326-6066 (ISSN-L)
- 2326-6074
- OpenAlex
- W2100413206
- Cited by
- 1,396
- References
- 12
- FWCI
- 29.30
- Type
- journal article
- Language
- en
- Open access
- bronze
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