ArticleBreast cancer research : BCR2010
Doxorubicin downregulates cell surface B7-H1 expression and upregulates its nuclear expression in breast cancer cells: role of B7-H1 as an anti-apoptotic molecule.
Article in Breast cancer research : BCR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
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Who cites it
136 citing papers in PubMed, 1 synthesis or guideline pooled it, 231 citations in OpenAlex.
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models).International journal of molecular sciences · 2021Pooled it
- The immune signatures predict gastric/gastroesophageal junction cancer response to first-line anti-PD-1 blockade or chemotherapy.BMC cancer · 2025Trial
- A phase II study of neoadjuvant atezolizumab and nab-paclitaxel in patients with anthracycline-resistant early-stage triple-negative breast cancer.Breast cancer research and treatment · 2023Trial
- Weekly Paclitaxel given concurrently with Durvalumab has a favorable safety profile in triple-negative metastatic breast cancer.Scientific reports · 2021Trial
- Nuclear PD-L1: an emerging oncogenic driver and promising therapeutic target in cancer.Journal of biomedical science · 2026Review
- Comparative effects of a TLR7/8 agonist and doxorubicin on immune checkpoint modulation and apoptosis in 4T1 breast cancer cells.Biochemistry and biophysics reports · 2026Article
- Evaluating Nuclear Levels of PD-L1 in Ovarian Cancer Cells by Western Blotting.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Intracellular PD-L1: Functions, Regulation, and Therapeutic Implications.International journal of biological sciences · 2026Review
- Suppression of tumor growth by GMI, an edible fungal immunomodulatory protein, is associated with targeting GSK3β‑mediated proteasomal degradation of PD‑L1.International journal of molecular medicine · 2025Article
- Notch1 Mutation Represents a Potential Therapeutic Target to Enhance Immune Recognition in Oral Squamous Cell Carcinoma.Cancer reports (Hoboken, N.J.) · 2025Article
- Cytotoxic Anti-tumor Drugs and Tumor-Associated Macrophages Synergistically Surge PD-L1 Expression in Esophageal Squamous Cell Carcinoma.Annals of surgical oncology · 2025Article
- PD-1/PD-L1 Inhibitors and Chemotherapy Synergy: Impact on Drug Resistance and PD-L1 Expression in Breast Cancer-Immune Cell Co-Cultures.International journal of molecular sciences · 2025Article
- Strategies to Overcome Intrinsic and Acquired Resistance to Chemoradiotherapy in Head and Neck Cancer.Cells · 2024Review
- IFNγ-Induced Bcl3, PD-L1 and IL-8 Signaling in Ovarian Cancer: Mechanisms and Clinical Significance.Cancers · 2024Review
- PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway.The Journal of experimental medicine · 2024Article
- Interaction of SMAC with a survivin-derived peptide alters essential cancer hallmarks: Tumor growth, inflammation, and immunosuppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- DRD1 suppresses cell proliferation and reduces EGFR activation and PD-L1 expression in NSCLC.Molecular oncology · 2024Article
- Regulatory mechanisms of PD-1/PD-L1 in cancers.Molecular cancer · 2024Review
- Beyond inhibition against the PD-1/PD-L1 pathway: development of PD-L1 inhibitors targeting internalization and degradation of PD-L1.RSC medicinal chemistry · 2024Review
- Notch signaling genes and CD8Cancer medicine · 2024Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionB7-H1 (PD-L1, CD274) is a T cell inhibitory molecule expressed in many types of cancer, leading to immune escape of tumor cells. Indeed, in previous reports we have shown an association of B7-H1 expression with high-risk breast cancer patients.
methodsIn the current study, we used immunohistochemistry, immunofluorescence and Western blot techniques to investigate the effect of neoadjuvant chemotherapy on the expression of B7-H1 in breast cancer cells.
resultsAmong tested chemotherapeutic agents, doxorubicin was the most effective in downregulating cell surface expression of B7-H1 in vitro. These results were validated in vivo in a xenograft mouse model, as well as in murine heart tissue known to constitutively express B7-H1. The doxorubicin-dependent cell surface downregulation of B7-H1 was accompanied by an upregulation of B7-H1 in the nucleus. This re-distribution of B7-H1 was concurrent with a similar translocation of phosphorylated AKT to the nucleus. Inhibition of the PI3K/AKT pathway abrogated the doxorubicin-mediated nuclear up-regulation of B7-H1, suggesting an involvement of PI3K/AKT pathway in the nuclear up-regulation of B7-H1. Interestingly, siRNA knock down of B7-H1 lead to an increase in spontaneous apoptosis, as well as doxorubicin-induced apoptosis, which indicates an anti-apoptotic role for B7-H1 in breast cancer cells. The novel discovery of B7-H1 expression in the nuclei of breast cancer cells suggests that B7-H1 has functions other than inhibition of T cells.
conclusionsOur findings explain the previously reported immunomodulatory effect of anthracyclines on cancer cells, and provide a link between immunoresistance and chemoresistance. Finally these results suggest the use of dual combinatorial agents to inhibit B7-H1 beside chemotherapy, in breast cancer patients.
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