ArticleJournal of immunology (Baltimore, Md. : 1950)2013
In vivo blockade of the programmed cell death-1 pathway using soluble recombinant PD-1-Fc enhances CD4+ and CD8+ T cell responses but has limited clinical benefit.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Expression Profile and Biological Role of Immune Checkpoints in Disease Progression of HIV/SIV Infection.Viruses · 2022Pooled it
- Review
- Real-world efficacy and safety of PD-1 inhibitors in patients living with HIV and cancer: a retrospective cohort study.Frontiers in oncology · 2026Article
- Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption.Nature immunology · 2024Article
- Targeting alternative splicing as a new cancer immunotherapy-phosphorylation of serine arginine-rich splicing factor (SRSF1) by SR protein kinase 1 (SRPK1) regulates alternative splicing of PD1 to generate a soluble antagonistic isoform that prevents T cell exhaustion.Cancer immunology, immunotherapy : CII · 2023Article
- Immune checkpoint inhibitors as potential therapy for reverting T-cell exhaustion and reverting HIV latency in people living with HIV.Frontiers in immunology · 2023Review
- Analysis of the mechanisms regulating soluble PD-1 production and function in human NK cells.Frontiers in immunology · 2023Article
- Serum soluble programmed death-1 levels predict the spontaneous HBeAg seroclearance in chronic hepatitis B.Journal of gastroenterology · 2022Article
- Soluble programmed cell death-1 predicts hepatocellular carcinoma development during nucleoside analogue treatment.Scientific reports · 2022Article
- TIGIT marks exhausted T cells and serves as a target for immune restoration in patients with chronic HBV infection.American journal of translational research · 2022Article
- Temporal and spatial characterization of negative regulatory T cells in HIV-infected/AIDS patients raises new diagnostic markers and therapeutic strategies.Journal of clinical laboratory analysis · 2021Article
- Characterization of soluble PD-L1 in pleural effusions of mesothelioma patients: potential implications in the immune response and prognosis.Journal of cancer research and clinical oncology · 2021Article
- Investigation of the PD-1 and PD-L1 Immune Checkpoint Molecules Throughout Healthy Human Pregnancy and in Nonpregnant Women.Journal of clinical medicine · 2020Article
- CD8Nature reviews. Immunology · 2020Review
- CTLA-4 and PD-1 dual blockade induces SIV reactivation without control of rebound after antiretroviral therapy interruption.Nature medicine · 2020Article
- Soluble PD-1: Predictive, Prognostic, and Therapeutic Value for Cancer Immunotherapy.Frontiers in immunology · 2020Review
- Cancer and HIV-1 Infection: Patterns of Chronic Antigen Exposure.Frontiers in immunology · 2020Review
- PD-1 Blockade and TLR7 Activation Lack Therapeutic Benefit in Chronic Simian Immunodeficiency Virus-Infected Macaques on Antiretroviral Therapy.Antimicrobial agents and chemotherapy · 2019Article
- Kynurenine 3-Monooxygenase Inhibition during Acute Simian Immunodeficiency Virus Infection Lowers PD-1 Expression and Improves Post-Combination Antiretroviral Therapy CD4Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Clinical significance of soluble forms of immune checkpoint molecules in advanced esophageal cancer.Medical oncology (Northwood, London, England) · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The programmed cell death-1 (PD-1)/programmed cell death ligand-1 pathway has been shown to limit cell-mediated effector functions during chronic viral infections impeding clearance of pathogens. As a strategy to reverse this exhaustion and increase T cell polyfunctionality, PD-1 ligands were blocked in vivo using a recombinant macaque PD-1 fused to a macaque Ig-Fc (rPD-1-Fc) in SIVmac239-infected rhesus macaques during the early chronic phase of infection, either alone or in combination with antiretroviral therapy. In vitro blockade showed improvement of Ag-specific CD4(+) and CD8(+) T cells from monkeys chronically infected with SIV. Of note, a prolonged 5-d blockade in culture was beneficial for both gag-specific CD4(+) and CD8(+) T cells based on proliferation and dual cytokine production. Although the in vivo administration of rPD-1-Fc induced enhanced SIV-specific CD4 and CD8 T cell proliferation both in the blood and gut, it failed to alter plasma viremia. However, rPD-1-Fc administration in the context of antiretroviral therapy interruption induced a significant delay of viral load rebound. In addition, rPD-1-Fc administration in MamuA*001(+) monkeys led to both an increase in the frequencies and Ki67 expression of GagCM9(+) CD8(+) T cells in the blood and rectal mucosa and polyfunctionality of GagCM9(+) CD8(+) T cells in blood. In conclusion, however, our data suggest that PD-1/programmed cell death ligand-1 blockade using soluble rPD-1-Fc instead of anti-PD-1 mAb, although effective in rescuing the effector function of SIV-specific CD4(+) and CD8(+) T cells during the early chronic phase of infection, has limited clinical benefit.
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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.