ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Th1 cytokine interferon gamma improves response in HER2 breast cancer by modulating the ubiquitin proteasomal pathway.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Intercepting Premalignant, Preinvasive Breast Lesions Through Vaccination.Frontiers in immunology · 2021Pooled it
- Beyond the dose: a clearance-enabled in vitro platform for evaluating local therapies.Drug delivery and translational research · 2026Article
- HSP90 shields ROC1/RBX1 from proteasomal degradation by CHIP E3 ubiquitin ligase to promote lung adenocarcinoma.Signal transduction and targeted therapy · 2026Article
- Intratumoral dendritic cell immunotherapy controls dissemination of metastasis-initiating cancer cells, even in patients with metastatic breast cancer.Journal for immunotherapy of cancer · 2026Article
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- IFNγ-induced antigen loss in chimeric antigen receptor-T cell therapy.Frontiers in immunology · 2026Article
- Pyrotinib inhibits the tumorigenicity of HER2-positive non-small cell lung cancer by inducing ARIH1/ubiquitin/lysosome-dependent degradation of HER2.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- CAND1 mediates CUL7-dependent HER2 protein stability to drive breast cancer progression.Breast cancer research : BCR · 2025Article
- Plasma IFN-γ may predict pyrotinib efficacy in patients with HER2-positive advanced breast cancer.Biomedical reports · 2025Article
- The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression.Neoplasia (New York, N.Y.) · 2025Article
- Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis.Journal of cancer research and clinical oncology · 2025Article
- Article
- Association of Proteasome Activity and Pool Heterogeneity with Markers Determining the Molecular Subtypes of Breast Cancer.Cancers · 2025Article
- Immunocytes in the tumor microenvironment: recent updates and interconnections.Frontiers in immunology · 2025Review
- CD19-targeted HSP90 inhibitor nanoparticle combined with TKIs reduces tumor burden and enhances T-cell immunity in murine B-cell malignancies.Theranostics · 2025Article
- IFN-gamma in the tumor microenvironment: dual roles in cancer progression and therapy.EXCLI journal · 2025Review
- Targeting Cancer: Microenvironment and Immunotherapy Innovations.International journal of molecular sciences · 2024Review
- Breast cancer immunotherapy: Realities and advances.Cancer innovation · 2024Review
- Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets.Experimental hematology & oncology · 2024Review
- The Role of CD4International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
HER2 breast cancer (BC) remains a significant problem in patients with locally advanced or metastatic BC. We investigated the relationship between T helper 1 (Th1) immune response and the proteasomal degradation pathway (PDP), in HER2-sensitive and -resistant cells. HER2 overexpression is partially maintained because E3 ubiquitin ligase Cullin5 (CUL5), which degrades HER2, is frequently mutated or underexpressed, while the client-protective co-chaperones cell division cycle 37 (Cdc37) and heat shock protein 90 (Hsp90) are increased translating to diminished survival. The Th1 cytokine interferon (IFN)-γ caused increased CUL5 expression and marked dissociation of both Cdc37 and Hsp90 from HER2, causing significant surface loss of HER2, diminished growth, and induction of tumor senescence. In HER2-resistant mammary carcinoma, either IFN-γ or Th1-polarizing anti-HER2 vaccination, when administered with anti-HER2 antibodies, demonstrated increased intratumor CUL5 expression, decreased surface HER2, and tumor senescence with significant therapeutic activity. IFN-γ synergized with multiple HER2-targeted agents to decrease surface HER2 expression, resulting in decreased tumor growth. These data suggest a novel function of IFN-γ that regulates HER2 through the PDP pathway and provides an opportunity to impact HER2 responses through anti-tumor immunity.
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Registered trials
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