ArticleJournal of immunology (Baltimore, Md. : 1950)2011
4-1BB signaling synergizes with programmed death ligand 1 blockade to augment CD8 T cell responses during chronic viral infection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed.
- Functional heterogeneity and plasticity in naïve CD8 T cells drive superior effector and memory responses.The Journal of experimental medicine · 2026Article
- Both soluble and cell surface CD137 expressed by Foxp3+ CD4 T cells restrain autoimmune diabetes.The Journal of experimental medicine · 2026Article
- Functional heterogeneity and plasticity in naïve CD8 T cells drive superior effector and memory responses.bioRxiv : the preprint server for biology · 2025Article
- Bispecific antibody for lung cancer: mechanisms and clinical insights.Frontiers in immunology · 2025Review
- ATG-101 Is a Tetravalent PD-L1×4-1BB Bispecific Antibody That Stimulates Antitumor Immunity through PD-L1 Blockade and PD-L1-Directed 4-1BB Activation.Cancer research · 2024Article
- Agonist Antibodies for Cancer Immunotherapy: History, Hopes, and Challenges.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- IL-15 boosts activated HBV core-specific CD8iScience · 2024Article
- Tumor-derived semaphorin 4A improves PD-1-blocking antibody efficacy by enhancing CD8Science advances · 2023Article
- Controlling viral inflammatory lesions by rebalancing immune response patterns.Frontiers in immunology · 2023Review
- Agonism of 4-1BB for immune therapy: a perspective on possibilities and complications.Frontiers in immunology · 2023Review
- Hierarchical transcriptional network governing heterogeneous T cell exhaustion and its implications for immune checkpoint blockade.Frontiers in immunology · 2023Review
- Immune checkpoints on T and NK cells in the context of HBV infection: Landscape, pathophysiology and therapeutic exploitation.Frontiers in immunology · 2023Review
- The foundations of immune checkpoint blockade and the ipilimumab approval decennial.Nature reviews. Drug discovery · 2022Review
- Nanobody-based CAR-T cells for cancer immunotherapy.Biomarker research · 2022Review
- Knowns and Unknowns about CAR-T Cell Dysfunction.Cancers · 2022Review
- A human CD137×PD-L1 bispecific antibody promotes anti-tumor immunity via context-dependent T cell costimulation and checkpoint blockade.Nature communications · 2021Article
- In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL.Molecular cancer therapeutics · 2021Review
- Fundamentals of T Cell Metabolism and Strategies to Enhance Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Sphingosine kinase 2 restricts T cell immunopathology but permits viral persistence.The Journal of clinical investigation · 2020Article
- Tumor necrosis family receptor superfamily member 9/tumor necrosis factor receptor-associated factor 1 pathway on hepatitis C viral persistence and natural history.World journal of hepatology · 2020Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
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Abstract
Previous studies have identified the inhibitory role that the programmed death 1 (PD-1) pathway plays during chronic infection. Blockade of this pathway results in rescue of viral-specific CD8 T cells, as well as reduction of viral loads in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). We tested the effect of combining PD ligand 1 (PD-L1) blockade with an agonistic regimen that induces 4-1BB costimulation during chronic LCMV infection. There is a boosting effect in the rescue of LCMV-specific CD8 T cell responses after dual treatment with PD-L1 blockade and 4-1BB agonistic Abs when the amount and timing of 4-1BB costimulation are carefully controlled. When PD-L1-blocking Abs are given together with a single low dose of anti-4-1BB agonistic Abs, there is an enhanced and stable expansion of viral-specific CD8 T cells. Conversely, when blocking Abs to PD-L1 are given with a repetitive high dose of anti-4-1BB, there is an initial synergistic expansion of viral-specific CD8 T cells by day 7, followed by dramatic apoptosis by day 14. Viral control paralleled CD8 T cell kinetics after dual treatment. By day 7 posttreatment, viral titers were lower in both of the combined regimens (compared with PD-L1 blockade alone). However, whereas the high dose of anti-4-1BB plus PD-L1 blockade resulted in rebound of viral titers to original levels, the low dose of anti-4-1BB plus PD-L1 blockade resulted in a stable reduction of viral loads. These findings demonstrate the importance of carefully manipulating the balance between activating and inhibitory signals to enhance T cell responses during chronic infection.
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Registered trials
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