ArticleJournal of immunology (Baltimore, Md. : 1950)2015
CD4 T Cell Depletion Substantially Augments the Rescue Potential of PD-L1 Blockade for Deeply Exhausted CD8 T Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- WTAP Accelerates Exhaustion of CD8Mediators of inflammation · 2025Article
- Interleukin-17 signaling influences CD8Oncoimmunology · 2023Article
- Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing.Frontiers in oncology · 2023Article
- Spatial transcriptomics demonstrates the role of CD4 T cells in effector CD8 T cell differentiation during chronic viral infection.Cell reports · 2022Article
- Knowns and Unknowns about CAR-T Cell Dysfunction.Cancers · 2022Review
- Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1Immunity · 2021Article
- Key role of the CCR2-CCL2 axis in disease modification in a mouse model of tauopathy.Molecular neurodegeneration · 2021Article
- Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity.Journal of experimental & clinical cancer research : CR · 2021Review
- Interrogating Adaptive Immunity Using LCMV.Current protocols in immunology · 2020Article
- Pulmonary endothelium-derived PD-L1 induced by the H9N2 avian influenza virus inhibits the immune response of T cells.Virology journal · 2020Article
- The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity.Cell research · 2020Review
- α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas.Journal for immunotherapy of cancer · 2019Article
- TLR4 signaling improves PD-1 blockade therapy during chronic viral infection.PLoS pathogens · 2019Article
- Striking a Balance-Cellular and Molecular Drivers of Memory T Cell Development and Responses to Chronic Stimulation.Frontiers in immunology · 2019Review
- Monitoring Patient Response to Pembrolizumab With Peripheral Blood Exhaustion Marker Profiles.Frontiers in medicine · 2019Article
- CD4 T Cell Affinity Diversity Is Equally Maintained during Acute and Chronic Infection.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Long-Term Persistence of Exhausted CD8 T Cells in Chronic Infection Is Regulated by MicroRNA-155.Cell reports · 2018Article
- Combined immunotherapy with anti-PDL-1/PD-1 and anti-CD4 antibodies cures syngeneic disseminated neuroblastoma.Scientific reports · 2017Article
- T regulatory cells are critical for the maintenance, anamnestic expansion and protection elicited by vaccine-induced CD8 T cells.Immunology · 2017Article
- CD8 T-cell regulation by T regulatory cells and the programmed cell death protein 1 pathway.Immunology · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In various models of chronic infections and cancers, blockade of the inhibitory programmed cell death-1 (PD-1) pathway has been shown to be promising at restoring immune function. However, there is not a complete understanding of the factors that influence responsiveness to programmed death-ligand 1 (PD-L1) blockade. In particular, it is currently unclear whether the efficacy of PD-L1 blockade is dependent on the stage of disease. In a model of chronic lymphocytic choriomeningitis virus infection in mice, we show that exhausted CD8 T cells during the late stage of infection are refractory to rescue by PD-L1 blockade. Interestingly, PD-L1 blockade during the late stage of infection resulted in a biased expansion of PD-1(+) CTLA-4(+) regulatory T cells (Tregs) over antiviral CD8 T cells. Although previous studies have shown that Treg ablation can enhance the immune rescue by PD-L1 blockade, this regimen may induce lethal autoimmunity. In this report, we show that PD-L1 blockade together with CD4 T cell depletion effectively rescued deeply exhausted CD8 T cells and enhanced antiviral control during the late stage of chronic infection without any associated mortality. These data demonstrate the pleiotropic effects of anti-PD-L1 therapy on both virus-specific CD8 T cells and Tregs, and suggest a novel strategy for effectively rescuing deeply exhausted CD8 T cells.
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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.