ArticleCancer gene therapy2014
Adenovirus expressing β2-microglobulin recovers HLA class I expression and antitumor immunity by increasing T-cell recognition.
Article in Cancer gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Elucidating DNA Damage-Dependent Immune System Activation.International journal of molecular sciences · 2025Review
- The screening, identification, design and clinical application of tumor-specific neoantigens for TCR-T cells.Molecular cancer · 2023Review
- HLA and tumour immunology: immune escape, immunotherapy and immune-related adverse events.Journal of cancer research and clinical oncology · 2023Review
- A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours.Frontiers in pharmacology · 2023Article
- Article
- Review
- Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response.Frontiers in immunology · 2022Review
- Interpretable systems biomarkers predict response to immune-checkpoint inhibitors.Patterns (New York, N.Y.) · 2021Article
- Investigating T Cell Immunity in Cancer: Achievements and Prospects.International journal of molecular sciences · 2021Review
- HLA class I loss in colorectal cancer: implications for immune escape and immunotherapy.Cellular & molecular immunology · 2021Review
- Review
- Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation.Frontiers in immunology · 2021Review
- Molecular Genetics of Relapsed Diffuse Large B-Cell Lymphoma: Insight into Mechanisms of Therapy Resistance.Cancers · 2020Review
- Role of Human Leukocyte Antigen System as A Predictive Biomarker for Checkpoint-Based Immunotherapy in Cancer Patients.International journal of molecular sciences · 2020Review
- Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer.Journal of pathology and translational medicine · 2019Article
- HLA-mediated tumor escape mechanisms that may impair immunotherapy clinical outcomes via T-cell activation.Oncology letters · 2017Article
- Rejection versus escape: the tumor MHC dilemma.Cancer immunology, immunotherapy : CII · 2017Review
- The urgent need to recover MHC class I in cancers for effective immunotherapy.Current opinion in immunology · 2016Review
- Inhibitors of histone deacetylase 1 reverse the immune evasion phenotype to enhance T-cell mediated lysis of prostate and breast carcinoma cells.Oncotarget · 2016Article
- Frequent HLA class I alterations in human prostate cancer: molecular mechanisms and clinical relevance.Cancer immunology, immunotherapy : CII · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Optimal tumor cell surface expression of human leukocyte antigen (HLA) class I molecules is essential for the presentation of tumor-associated peptides to T-lymphocytes. However, a hallmark of many types of tumor is the loss or downregulation of HLA class I expression associated with ineffective tumor antigen presentation to T cells. Frequently, HLA loss can be caused by structural alterations in genes coding for HLA class I complex, including the light chain of the complex, β2-microglobulin (β2m). Its best-characterized function is to interact with HLA heavy chain and stabilize the complex leading to a formation of antigen-binding cleft recognized by T-cell receptor on CD8+ T cells. Our previous study demonstrated that alterations in the β2m gene are frequently associated with cancer immune escape leading to metastatic progression and resistance to immunotherapy. These types of defects require genetic transfer strategies to recover normal expression of HLA genes. Here we characterize a replication-deficient adenoviral vector carrying human β2m gene, which is efficient in recovering proper tumor cell surface HLA class I expression in β2m-negative tumor cells without compromising the antigen presentation machinery. Tumor cells transduced with β2m induced strong activation of T cells in a peptide-specific HLA-restricted manner. Gene therapy using recombinant adenoviral vectors encoding HLA genes increases tumor antigen presentation and represents a powerful tool for modulation of tumor cell immunogenicity by restoration of missing or altered HLA genes. It should be considered as part of cancer treatment in combination with immunotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.