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Original Articles
- Breast cancer
- The Association of Estrogen Receptor Activity, Interferon Signaling, and MHC Class I Expression in Breast Cancer
- In Hye Song, Young-Ae Kim, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, Yeon ho Choi, Heejae Lee, Jeong-Han Seo, Youngjin Cho, Sung Wook Jung, Hee Jeong Kim, Sei Hyun Ahn, Hee Jin Lee, Gyungyub Gong
- Cancer Res Treat. 2022;54(4):1111-1120. Published online December 21, 2021
- DOI: https://doi.org/10.4143/crt.2021.1017
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Abstract
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Supplementary Material
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ePub - Purpose
The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling.
Materials and Methods
The human leukocyte antigen (HLA)-ABC protein expression was analyzed in breast cancer cell lines. The expressions of HLA-A and MxA mRNAs were analyzed in MCF-7 cells in Gene Expression Omnibus (GEO) data. ER and HLA-ABC expressions, Ki-67 labeling index and TIL levels in tumor tissue were also analyzed in ER+/ human epidermal growth factor receptor 2 (HER2)- breast cancer patients who randomly received either neoadjuvant chemotherapy or estrogen modulator treatment followed by resection.
Results
HLA-ABC protein expression was decreased after β-estradiol treatment or hESR-GFP transfection and increased after fulvestrant or IFN-γ treatment in cell lines. In GEO data, HLA-A and MxA expression was increased after ESR1 shRNA transfection. In patients, ER Allred score was significantly lower and the HLA-ABC expression, TIL levels, and Ki-67 were significantly higher in the estrogen modulator treated group than the chemotherapy treated group.
Conclusion
MHC I expression and TIL levels might be affected by ER pathway modulation and IFN treatment. Further studies elucidating the mechanism of MHC I regulation could suggest a way to boost TIL influx in cancer in a clinical setting. -
Citations
Citations to this article as recorded by
- The Immunoregulatory Roles of ERα in Breast Cancer: Mechanisms, Crosstalk, and Therapeutic Insights
Afsoon Dehghani
Journal of Cancer Prevention.2026; 31(1): 1. CrossRef - Identifying Safeguards Disabled by Epstein-Barr Virus Infections in Genomes From Patients With Breast Cancer: Chromosomal Bioinformatics Analysis
Bernard Friedenson
JMIRx Med.2025; 6: e50712. CrossRef - Progesterone receptor-dependent downregulation of MHC class I promotes tumor immune evasion and growth in breast cancer
Julio C Tinoco, Harmony I Saunders, Lauryn Rose Werner, Xiaopeng Sun, Eilidh I Chowanec, Amanda Heard, Prabhakar Chalise, Jeffery M Vahrenkamp, Andrea E Wilson, Cong-Xiao Liu, Gangjun Lei, Junping Wei, Hugo Cros, Hisham Mohammed, Melissa Troester, Charles
Journal for ImmunoTherapy of Cancer.2025; 13(3): e010179. CrossRef - Neoadjuvant Chemotherapy Efficacy in Breast Cancer: Insights from Magnetic Resonance Imaging Compilation (MAGIC)
Honghong Wu, Zebo Huang, Jie Wang
Academic Radiology.2025; 32(8): 4369. CrossRef - Prenatal Bisphenol B Exposure Induces Adult Male Offspring Reproductive Dysfunction via ERα Inhibition-Triggered MHC I-Mediated Testicular Immunological Responses
Nannan Chen, Xiaotian Li, Shenrui Zhou, Xin Peng, Senlin Xue, Yuetong Liu, Tingwang Jiang, Wei Yan
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International Journal of Molecular Sciences.2025; 26(23): 11596. CrossRef - Toxic Epidermal Necrolysis and Steven–Johnson Syndrome During the Postpartum Period: A Literature Review with a Rare Case Presentation
Natalia Katarzyna Mazur-Ejankowska, Maciej Ejankowski, Magdalena Emilia Grzybowska, Jakub Żółkiewicz, Ewa Gostkowska, Wioletta Barańska-Rybak, Dariusz Grzegorz Wydra
Journal of Clinical Medicine.2025; 15(1): 17. CrossRef - Estrogen receptor regulation of the immune microenvironment in breast cancer
Conor McGuinness, Kara L. Britt
The Journal of Steroid Biochemistry and Molecular Biology.2024; 240: 106517. CrossRef - Bioinformatic-Experimental Screening Uncovers Multiple Targets for Increase of MHC-I Expression through Activating the Interferon Response in Breast Cancer
Xin Li, Zilun Ruan, Shuzhen Yang, Qing Yang, Jinpeng Li, Mingming Hu
International Journal of Molecular Sciences.2024; 25(19): 10546. CrossRef - Hormone Receptor Signaling and Breast Cancer Resistance to Anti-Tumor Immunity
Alexandra Moisand, Mathilde Madéry, Thomas Boyer, Charlotte Domblides, Céline Blaye, Nicolas Larmonier
International Journal of Molecular Sciences.2023; 24(20): 15048. CrossRef
- The Immunoregulatory Roles of ERα in Breast Cancer: Mechanisms, Crosstalk, and Therapeutic Insights
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- 198 Download
- 11 Web of Science
- 12 Crossref
- An Antibody Against E2 / MIC2 Antigen ( CD99 ) : Indentification and Characterization
- Kyeong Cheon Jung, Tae Jin Kim, Doo Hyun Chung, Kuhn Kuk Lee, Jang Hee Hahm, Seong Hoe Park
- J Korean Cancer Assoc. 1996;28(2):350-358.
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Abstract
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- Liposome-mediated gene transfer offers the potential to introduce DNA encoding therapeutic DNA to treat human disease. Several genes have been used in gene therapy to stimulate immune response in malignancy, and allogeneic major histocompatibility complex (MHC) proteins also serve as a potent stimulus to the immune system. This study was performed to determine the transfection efficiency and safety of liposome- mediated gene delivery into human cancer cell lines and animals. Placental alkaline phosphatase gene as a reporter was transfected into PCI-13 and NCI-H522 cell lines, and the expression was determined in individual transfected cells by histochemical staining. The transfectian efficiency was the highest at 24 ￥ig of DNA mixed with 10￥il of lipofectamine in vitro, HLA-B7 DNA as a therapeutic gene was transfected into cell lines and injected subcutaneously into the rabbits. The HLA-B7 gene expression was successfully identified by RT-PCR in vivo and in vitro. Twenty percents of the cells expressed HLA-B7 proteins which were analyzed by flow cytometry. In rabbit model, no pyrogenic response was ob- served after subcutaneous injection of HLA-B7/liposome complexes. The expression of injected HLA-B7 gene was restricted within the injected skin. These data showed the feasibility and safety of liposome-mediated gene transfer. These findings will provide a basis to develop strategies for the gene therapy of human cancer.
- 3,036 View
- 17 Download
- Preclinical Study of HLA-B7 DNA / Liposome Complex for Gene Therapy
- Seong Jun Yoon, Won Seok Kim, Jae Go Seol, Sagn Goo Lee, Kee Hyung Lee, Dae Seog Heo, Noe Kyeong Kim
- J Korean Cancer Assoc. 1996;28(2):358-368.
- 2,871 View
- 14 Download
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