ArticleJournal of immunology (Baltimore, Md. : 1950)2012
B7-DC-Ig enhances vaccine effect by a novel mechanism dependent on PD-1 expression level on T cell subsets.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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
26 citing papers in PubMed, 47 citations in OpenAlex.
- Generating immunogenomic data-guided virtual patients using a QSP model to predict response of advanced NSCLC to PD-L1 inhibition.NPJ precision oncology · 2023Article
- Generating immunogenomic data-guided virtual patients using a QSP model to predict response of advanced NSCLC to PD-L1 inhibition.bioRxiv : the preprint server for biology · 2023Article
- Laparoscopic-Assisted Colorectal Resection Can Reduce the Inhibition of Immune Function Compared with Conventional Open Surgery: A Retrospective Clinical Study.Journal of clinical medicine · 2023Article
- Article
- L2pB1 Cells Contribute to Tumor Growth Inhibition.Frontiers in immunology · 2021Article
- T cells with high PD-1 expression are associated with lower HIV-specific immune responses despite long-term antiretroviral therapy.AIDS (London, England) · 2020Article
- Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response.Clinical and experimental hepatology · 2019Article
- Review
- Prokaryotic expression of the extracellular domain of porcine programmed death 1 (PD-1) and its ligand PD-L1 and identification of the binding with peripheral blood mononuclear cellsCanadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2017Article
- Posttranscriptional Control of PD-L1 Expression by 17β-Estradiol via PI3K/Akt Signaling Pathway in ERα-Positive Cancer Cell Lines.International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2017Article
- PD-L1-specific T cells.Cancer immunology, immunotherapy : CII · 2016Review
- Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014.Journal of translational medicine · 2015Article
- Development of PD-1/PD-L1 Pathway in Tumor Immune Microenvironment and Treatment for Non-Small Cell Lung Cancer.Scientific reports · 2015Review
- ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T lymphocytes for enhanced anti-tumor immunotherapy.EMBO molecular medicine · 2015Article
- Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway.Trends in molecular medicine · 2015Review
- Human Cancer Immunotherapy with PD-1/PD-L1 Blockade.Biomarkers in cancer · 2015Review
- Animal models for viral infection and cell exhaustion.Current opinion in HIV and AIDS · 2014Review
- Considerations for combined immune checkpoint modulation and radiation treatment.Radiation research · 2014Review
- Influence of PD-L1 cross-linking on cell death in PD-L1-expressing cell lines and bovine lymphocytes.Immunology · 2014Article
- RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance.The Journal of experimental medicine · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Programmed death receptor 1 (PD-1) is an important signaling molecule often involved in tumor-mediated suppression of activated immune cells. Binding of this receptor to its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), attenuates T cell activation, reduces IL-2 and IFN-γ secretion, decreases proliferation and cytotoxicity, and induces apoptosis. B7-DC-Ig is a recombinant protein that binds and targets PD-1. It is composed of an extracellular domain of murine B7-DC fused to the Fc portion of murine IgG2a. In this study, we demonstrate that B7-DC-Ig can enhance the therapeutic efficacy of vaccine when combined with cyclophosphamide. We show that this combination significantly enhances Ag-specific immune responses and leads to complete eradication of established tumors in 60% of mice and that this effect is CD8 dependent. We identified a novel mechanism by which B7-DC-Ig exerts its therapeutic effect that is distinctly different from direct blocking of the PD-L1-PD-1 interaction. In this study, we demonstrate that there are significant differences between levels and timing of surface PD-1 expression on different T cell subsets. We found that these differences play critical roles in anti-tumor immune effect exhibited by B7-DC-Ig through inhibiting proliferation of PD-1(high) CD4 T cells, leading to a significant decrease in the level of these cells, which are enriched for regulatory T cells, within the tumor. In addition, it also leads to a decrease in PD-1(high) CD8 T cells, tipping the balance toward nonexhausted functional PD-1(low) CD8 T cells. We believe that the PD-1 expression level on T cells is a crucial factor that needs to be considered when designing PD-1-targeting immune therapies.
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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.