ArticleJournal of immunology (Baltimore, Md. : 1950)2005
Immune selection of hot-spot beta 2-microglobulin gene mutations, HLA-A2 allospecificity loss, and antigen-processing machinery component down-regulation in melanoma cells derived from recurrent metastases following immunotherapy.
Article in Journal of immunology (Baltimore, Md. : 1950), 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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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
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis.Molecular diagnosis & therapy · 2023Pooled it
- Interferons and Resistance Mechanisms in Tumors and Pathogen-Driven Diseases-Focus on the Major Histocompatibility Complex (MHC) Antigen Processing Pathway.International journal of molecular sciences · 2023Review
- A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours.Frontiers in pharmacology · 2023Article
- Immunosuppressive Signaling Pathways as Targeted Cancer Therapies.Biomedicines · 2022Review
- The immune-related role of beta-2-microglobulin in melanoma.Frontiers in oncology · 2022Review
- MHC Class I Deficiency in Solid Tumors and Therapeutic Strategies to Overcome It.International journal of molecular sciences · 2021Review
- Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation.Frontiers in immunology · 2021Review
- Role of Human Leukocyte Antigen System as A Predictive Biomarker for Checkpoint-Based Immunotherapy in Cancer Patients.International journal of molecular sciences · 2020Review
- Review
- Genetic and epigenetic analysis of the beta-2-microglobulin gene in microsatellite instable colorectal cancer.Clinical and experimental medicine · 2020Article
- The Double-Edge Sword of Autophagy in Cancer: From Tumor Suppression to Pro-tumor Activity.Frontiers in oncology · 2020Review
- Alternative mRNA splicing in cancer immunotherapy.Nature reviews. Immunology · 2019Review
- STING Signaling in Melanoma Cells Shapes Antigenicity and Can Promote Antitumor T-cell Activity.Cancer immunology research · 2019Article
- Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy.Cancer immunology, immunotherapy : CII · 2019Review
- 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
- Using single nucleotide variations in single-cell RNA-seq to identify subpopulations and genotype-phenotype linkage.Nature communications · 2018Article
- Acquired resistance to immunotherapy in MMR-D pancreatic cancer.Journal for immunotherapy of cancer · 2018Article
- Defective HLA class I antigen processing machinery in cancer.Cancer immunology, immunotherapy : CII · 2018Article
- Article
- Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines.Journal of immunology research · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Scanty information is available about the mechanisms underlying HLA class I Ag abnormalities in malignant cells exposed to strong T cell-mediated selective pressure. In this study, we have characterized the molecular defects underlying HLA class I Ag loss in five melanoma cell lines derived from recurrent metastases following initial clinical responses to T cell-based immunotherapy. Point mutations in the translation initiation codon (ATG-->ATA) and in codon 31 (TCA-->TGA) of the beta(2)-microglobulin (beta(2)m) gene were identified in the melanoma cell lines 1074MEL and 1174MEL, respectively. A hot-spot CT dinucleotide deletion within codon 13-15 was found in the melanoma cell lines 1106MEL, 1180MEL, and 1259MEL. Reconstitution of beta(2)m expression restored HLA class I Ag expression in the five melanoma cell lines; however, the HLA-A and HLA-B,-C gene products were differentially expressed by 1074MEL, 1106MEL, and 1259MEL cells. In addition, in 1259MEL cells, the Ag-processing machinery components calnexin, calreticulin, and low m.w. polypeptide 10 are down-regulated, and HLA-A2 Ags are selectively lost because of a single cytosine deletion in the HLA-A2 gene exon 4. Our results in conjunction with those in the literature suggest the emergence of a preferential beta(2)m gene mutation in melanoma cells following strong T cell-mediated immune selection. Furthermore, the presence of multiple HLA class I Ag defects within a tumor cell population may reflect the accumulation of multiple escape mechanisms developed by melanoma cells to avoid distinct sequential T cell-mediated selective events.
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Registered trials
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