ArticleBreast cancer research : BCR2023
The loss of B7-H4 expression in breast cancer cells escaping from T cell cytotoxicity contributes to epithelial-to-mesenchymal transition.
Article in Breast cancer research : BCR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed.
- Knowledge mapping and research trends of chimeric antigen receptor T-cell immunotherapy in breast cancer: A bibliometric and visual analytics study.Human vaccines & immunotherapeutics · 2026Article
- The absence of B7-H4 inhibits PD-L1 expression by driving a methylation of PD-L1 promoter in breast cancer cells.Breast cancer research : BCR · 2026Article
- Fully human anti-B7-H4 antibody induces lysosome-dependent ferroptosis to reverse primary resistance to PD-1 blockade.Journal for immunotherapy of cancer · 2026Article
- B7-H4: a multifaceted immune checkpoint and oncoprotein in cancer biology and immunotherapy.Frontiers in immunology · 2026Review
- Article
- Investigation of the Effects of B7H4 (rs10754339 A>G) Gene Polymorphism and Serum Level on Breast Cancer Susceptibility.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Epithelial-to-mesenchymal transition (EMT) and cancer metastasis: the status quo of methods and experimental models 2025.Molecular cancer · 2025Review
- B7 Homolog 4 (B7-H4)-Directed Agents in Oncology Clinical Trials: A Review.Journal of immunotherapy and precision oncology · 2025Review
- Current status and innovative developments of CAR-T-cell therapy for the treatment of breast cancer.Cancer cell international · 2025Review
- The Trojan Horse Within: Mechanisms of Immune Evasion in Breast Cancer.Cancer heterogeneity and plasticity · 2025Article
- Immune evasion and resistance in breast cancer.American journal of cancer research · 2025Review
- Multiomics2Targets identifies targets from cancer cohorts profiled with transcriptomics, proteomics, and phosphoproteomics.Cell reports methods · 2024Article
- Epithelial-mesenchymal plasticity in cancer: signaling pathways and therapeutic targets.MedComm · 2024Review
- B7H4 Role in Solid Cancers: A Review of the Literature.Cancers · 2024Review
- Differential Immune Checkpoint Protein Expression in HNSCC: The Role of HGF/MET Signaling.International journal of molecular sciences · 2024Article
- CAR-based immunotherapy for breast cancer: peculiarities, ongoing investigations, and future strategies.Frontiers in immunology · 2024Review
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Abstract
backgroundB7 homology 4 (B7-H4), a potential target for cancer therapy, has been demonstrated to inhibit T cell cytotoxicity in the early stages of breast cancer. However, B7-H4 manipulating breast tumor immune microenvironment (TIME) in the tumor progression remains unknown.
methodsWe engineered T cells with B7-H4-specific chimeric antigen receptors (CARs) and performed a T cell co-culture assay to characterize B7-H4 expression level in breast cancer cells escaping from T cell cytotoxicity. We generated B7-H4 knockout (KO) and overexpression (OE) breast cancer cells to determine the epithelial-to-mesenchymal transition (EMT) and stemness characteristics in vitro and in vivo, including tumor proliferation, migration, metastasis and chemoresistance. The Cancer Genome Atlas breast cancer database was accessed to investigate the correlation between B7-H4 expression levels and EMT characteristics in patients with breast cancer.
resultsOur result found that B7-H4 expression level was significantly reduced in a subset of breast cancer cells that escaped from the cytotoxicity of B7-H4 CAR-T cells. Compared with wild type cells, B7-H4 KO cells prompt EMT and stemness characteristics, including migration, invasion and metastasis, and OE cells vice versa. The increase in H3K27me3 in KO cells confirmed the epigenetic reprogramming of cancer stem cells. The IC50 of doxorubicin or oxaliplatin significantly increased in KO cells, which was in agreement with a decrease in OE cells. Moreover, a trend of downregulated B7-H4 from stage I to stage II breast cancer patients indicates that the low-expressing B7-H4 breast cancer cells escaping from TIME have spread to nearby breast lymph nodes in the cancer progression.
conclusionsOur study illuminates the novel role of renouncing B7-H4 in breast cancer cells through immune escape, which contributes to EMT processes and provides new insights for breast cancer treatments.
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