ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Ubiquitin-like Molecule ISG15 Acts as an Immune Adjuvant to Enhance Antigen-specific CD8 T-cell Tumor Immunity.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
- Dendritic cell vaccines targeting tumor blood vessel antigens in combination with dasatinib induce therapeutic immune responses in patients with checkpoint-refractory advanced melanoma.Journal for immunotherapy of cancer · 2021Trial
- A Spatial Atlas of Muscle-Invasive Bladder Cancer Reveals Lineage-Specific Vulnerabilities and Immune Architecture.Cancer discovery · 2026Article
- Spleen-targeted neoantigen mRNA vaccine induces ISG15Cell reports. Medicine · 2026Article
- Cell-Intrinsic Type I Interferon Signaling as a Pleiotropic Orchestrator of CD4 T Cell Immunity.Biomolecules · 2026Review
- Chronic ISG15 Exposure Accelerates CD8+ T-cell Dysfunction while Increasing PD-1 Blockade Sensitivity in Oral Squamous Cell Carcinoma.Cancer immunology research · 2025Article
- ISG15 as a Potent Immune Adjuvant in MVA-Based Vaccines Against Zika Virus and SARS-CoV-2.Vaccines · 2025Article
- Short IL-18 generated by caspase-3 cleavage mobilizes NK cells to suppress tumor growth.Nature immunology · 2025Article
- Interferon-stimulated gene subtypes as key indicators of immune landscape and survival outcomes in ovarian cancer.Discover oncology · 2024Article
- Review
- Unveiling the Multifaceted Roles of ISG15: From Immunomodulation to Therapeutic Frontiers.Vaccines · 2024Review
- ISG15-LFA1 interactions in latent HIV clearance: mechanistic implications in designing antiviral therapies.Frontiers in cell and developmental biology · 2024Article
- DNA and RNA vaccines against tuberculosis: a scoping review of human and animal studies.Frontiers in immunology · 2024Article
- Antagonism of regulatory ISGs enhances the anti-melanoma efficacy of STING agonists.Frontiers in immunology · 2024Article
- Single-Cell RNA Sequencing Reveals Immuno-Oncology Characteristics of Tumor-Infiltrating T Lymphocytes in Photodynamic Therapy-Treated Colorectal Cancer Mouse Model.International journal of molecular sciences · 2023Article
- ISG15: A link between innate immune signaling, DNA replication, and genome stability.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- The future of cancer immunotherapy: DNA vaccines leading the way.Medical oncology (Northwood, London, England) · 2023Review
- ISG15 targets glycosylated PD-L1 and promotes its degradation to enhance antitumor immune effects in lung adenocarcinoma.Journal of translational medicine · 2023Article
- Article
- An expanded lexicon for the ubiquitin code.Nature reviews. Molecular cell biology · 2023Review
- The Functional Roles of ISG15/ISGylation in Cancer.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
ISG15 is an ubiquitin-like protein induced by type I interferon associated with antiviral activity. ISG15 is also secreted and known to function as an immunomodulatory molecule. However, ISG15's role in influencing the adaptive CD8 T-cell responses has not been studied. Here, we demonstrate the efficacy of ISG15 as a vaccine adjuvant, inducing human papilloma virus (HPV) E7-specific IFNγ responses as well as the percentage of polyfunctional, cytolytic, and effector CD8 T-cell responses. Vaccination with ISG15 conferred remarkable control and/or regression of established HPV-associated tumor-bearing mice. T-cell depletion coupled with adoptive transfer experiments revealed that ISG15 protective efficacy was CD8 T-cell mediated. Importantly, we demonstrate that ISG15 vaccine-induced responses could be generated independent of ISGylation, suggesting that responses were mostly influenced by free ISG15. Our results provide more insight into the immunomodulatory properties of ISG15 and its potential to serve as an effective immune adjuvant in a therapeutic tumor or infectious disease setting.
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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.