ArticlePloS one2016
Poxvirus-Based Active Immunotherapy with PD-1 and LAG-3 Dual Immune Checkpoint Inhibition Overcomes Compensatory Immune Regulation, Yielding Complete Tumor Regression in Mice.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- Effectiveness and safety of PD-1/L1 inhibitors as first-line therapy for patients with advanced or metastatic urothelial carcinoma who are ineligible for platinum-based chemotherapy: a meta-analysis.Frontiers in immunology · 2025Pooled it
- Effect of neoadjuvant chemotherapy on tumor immune infiltration in breast cancer patients: Systematic review and meta-analysis.PloS one · 2023Pooled it
- Phase II trial of CV301 vaccine combined with atezolizumab in advanced urothelial carcinoma.Cancer immunology, immunotherapy : CII · 2023Trial
- Tobemstomig, a Novel Bispecific Antibody, Preferentially Blocks PD-1 and LAG-3 on CD8 TILs to Expand Stem-like T Cells for Sustained Tumor Control.Cancer research communications · 2026Article
- Immunotherapy Resistance and Therapeutic Strategies in PD-L1 High Expression Non-Small Cell Lung Cancer.OncoTargets and therapy · 2025Review
- Nasopharyngeal Carcinoma and Its Microenvironment: Past, Current, and Future Perspectives.Frontiers in oncology · 2022Review
- Disruption of Her2-Induced PD-L1 Inhibits Tumor Cell Immune Evasion in Patient-Derived Gastric Cancer Organoids.Cancers · 2021Article
- Immune Checkpoints, Inhibitors and Radionuclides in Prostate Cancer: Promising Combinatorial Therapy Approach.International journal of molecular sciences · 2021Review
- Synergistic cancer immunotherapy combines MVA-CD40L induced innate and adaptive immunity with tumor targeting antibodies.Nature communications · 2019Article
- Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups.Nature immunology · 2019Review
- Resistance mechanisms in melanoma to immuneoncologic therapy with checkpoint inhibitors.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Roles, function and relevance of LAG3 in HIV infection.PLoS pathogens · 2019Review
- Gene module analysis of juvenile myelomonocytic leukemia and screening of anticancer drugs.Oncology reports · 2018Article
- Present and future of cancer immunotherapy: A tumor microenvironmental perspective.Oncology letters · 2018Review
- Lymphocyte-Activation Gene-3 Expression and Prognostic Value in Neoadjuvant-Treated Triple-Negative Breast Cancer.Journal of breast cancer · 2018Article
- Immune-checkpoint inhibitors for combating T-cell dysfunction in cancer.OncoTargets and therapy · 2018Review
- Blockade of LAG-3 Immune Checkpoint Combined With Therapeutic Vaccination Restore the Function of Tissue-Resident Anti-viral CD8Frontiers in immunology · 2018Observational
- 5T4 oncofoetal glycoprotein: an old target for a novel prostate cancer immunotherapy.Oncotarget · 2017Article
- LAG3 (CD223) as a cancer immunotherapy target.Immunological reviews · 2017Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poxvirus-based active immunotherapies mediate anti-tumor efficacy by triggering broad and durable Th1 dominated T cell responses against the tumor. While monotherapy significantly delays tumor growth, it often does not lead to complete tumor regression. It was hypothesized that the induced robust infiltration of IFNγ-producing T cells into the tumor could provoke an adaptive immune evasive response by the tumor through the upregulation of PD-L1 expression. In therapeutic CT26-HER-2 tumor models, MVA-BN-HER2 poxvirus immunotherapy resulted in significant tumor growth delay accompanied by a robust, tumor-infiltrating T cell response that was characterized by low to mid-levels of PD-1 expression on T cells. As hypothesized, this response was countered by significantly increased PD-L1 expression on the tumor and, unexpectedly, also on infiltrating T cells. Synergistic benefit of anti-tumor therapy was observed when MVA-BN-HER2 immunotherapy was combined with PD-1 immune checkpoint blockade. Interestingly, PD-1 blockade stimulated a second immune checkpoint molecule, LAG-3, to be expressed on T cells. Combining MVA-BN-HER2 immunotherapy with dual PD-1 plus LAG-3 blockade resulted in comprehensive tumor regression in all mice treated with the triple combination therapy. Subsequent rejection of tumors lacking the HER-2 antigen by treatment-responsive mice without further therapy six months after the original challenge demonstrated long lasting memory and suggested that effective T cell immunity to novel, non-targeted tumor antigens (antigen spread) had occurred. These data support the clinical investigation of this triple therapy regimen, especially in cancer patients harboring PD-L1neg/low tumors unlikely to benefit from immune checkpoint blockade alone.
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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.