ArticleThe Journal of experimental medicine2023
An oncolytic virus-delivered TGFβ inhibitor overcomes the immunosuppressive tumor microenvironment.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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The trial behind it
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
40 citing papers in PubMed, 39 citations in OpenAlex.
- In situ APMV-4 vaccination primes systemic response to subtherapeutic dosing of aCTLA-4 in colorectal carcinoma.Journal for immunotherapy of cancer · 2026Article
- Intravenously deliverable oncolytic virus VET3-TGI favorably alters the tumor microenvironment.Journal for immunotherapy of cancer · 2026Article
- Delivery Strategies for Oncolytic Viruses in Gastrointestinal Cancers: Progress, Mechanisms and Clinical Translations.Reviews in medical virology · 2026Review
- Recent advances in oncolytic virotherapy: insights from clinical trials and combination treatment strategies.Virology journal · 2026Review
- Recent advances in TGF-β signaling: insights into regulation, pathophysiological function, and clinical translation.Cell regeneration (London, England) · 2026Article
- Bridging mechanism and clinic: unlocking the full potential of oncolytic virus-based immunotherapy.Molecular cancer · 2026Review
- Stratifying tumor immune microenvironment in head and neck squamous cell carcinoma: from parsing out immune-subtype prognosis to clinically applicable CT-radiomics models.Journal of translational medicine · 2026Article
- Oncolytic viruses: advanced strategies in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Divergent role of CD8 T cells with distinct metabolic phenotypes during curative radio-immunotherapy in hot versus cold tumors.bioRxiv : the preprint server for biology · 2026Article
- Short-term efficacy and safety of recombinant human adenovirus type 5 combined with PD-1 immune checkpoint inhibitors and SOX regimen in neoadjuvant therapy of locally advanced gastric cancer: a retrospective study.Frontiers in oncology · 2026Article
- Dual Graphene Oxide-Based Multigene Delivery for Cancer Elimination via Stromal and Immune Reprogramming.International journal of biomaterials · 2026Article
- Oncolytic viruses in head and neck cancer: therapeutic promise and translational challenges.Frontiers in immunology · 2026Review
- Advancements in intratumoral therapies for liver tumors.Frontiers in oncology · 2026Review
- Oncolytic adenovirus encoding a TGF-β inhibitor synergizes with PD-1 blockade to potentiate NK cell cytotoxicity against NSCLC.Frontiers in immunology · 2026Article
- Advances in protein ubiquitination modification and immune evasion of breast cancer.Frontiers in cell and developmental biology · 2026Review
- Review
- Advances in augmenting infiltration of active natural killer cells into pediatric and adult solid tumors.Molecular therapy. Oncology · 2025Review
- Targeting hepatocytic TβRI ameliorates liver metastatic outcomes by revitalizing stem-like CD8Nature communications · 2025Article
- TIM-3 blockade reverses oncolytic vaccinia virus-induced DCs inactivation and T cells exhaustion to improve antitumor immunity and therapeutic efficacy.Journal of experimental & clinical cancer research : CR · 2025Article
- Oncolytic Virotherapy in Solid Tumors: A Current Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
While checkpoint blockade immunotherapies have widespread success, they rely on a responsive immune infiltrate; as such, treatments enhancing immune infiltration and preventing immunosuppression are of critical need. We previously generated αPD-1 resistant variants of the murine HNSCC model MEER. While entirely αPD-1 resistant, these tumors regress after single dose of oncolytic vaccinia virus (VV). We then generated a VV-resistant MEER line to dissect the immunologic features of sensitive and resistant tumors. While treatment of both tumor types induced immune infiltration and IFNγ, we found a defining feature of resistance was elevation of immunosuppressive cytokines like TGFβ, which blunted IFNγ signaling, especially in regulatory T cells. We engineered VV to express a genetically encoded TGFβRII inhibitor. Inhibitor-expressing VV produced regressions in resistant tumor models and showed impressive synergy with checkpoint blockade. Importantly, tumor-specific, viral delivery of TGFβ inhibition had no toxicities associated with systemic TGFβ/TGFβR inhibition. Our data suggest that aside from stimulating immune infiltration, oncolytic viruses are attractive means to deliver agents to limit immunosuppression in cancer.
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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.