ArticlePLoS pathogens2019
TLR4 signaling improves PD-1 blockade therapy during chronic viral infection.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
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- NLRP3 and AIM2 inflammasomes exacerbate the pathogenic Th17 cell response to eggs of the helminth Schistosoma mansoni.PLoS pathogens · 2025Article
- TLR4/MyD88 expression patterns and novel genetic variants: association with aggressive clinicopathological features in colorectal cancer.Frontiers in oncology · 2025Article
- An HIV-1 CRISPR-Cas9 membrane trafficking screen reveals a role for PICALM intersecting endolysosomes and immunity.iScience · 2024Article
- An attenuated lymphocytic choriomeningitis virus vector enhances tumor control in mice partly via IFN-I.The Journal of clinical investigation · 2024Article
- Feasibility of Using a Type I IFN-Based Non-Animal Approach to Predict Vaccine Efficacy and Safety Profiles.Vaccines · 2024Review
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- Prediction of biomarkers and therapeutic combinations for anti-PD-1 immunotherapy using the global gene network association.Nature communications · 2022Article
- Adoptive B cell therapy for chronic viral infection.Frontiers in immunology · 2022Article
- Fractionating a COVID-19 Ad5-vectored vaccine improves virus-specific immunity.Science immunology · 2021Article
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- Reversal of the CD8Frontiers in immunology · 2021Article
- Early type I IFN blockade improves the efficacy of viral vaccines.The Journal of experimental medicine · 2020Article
- Interrogating Adaptive Immunity Using LCMV.Current protocols in immunology · 2020Article
- Review
- Pembrolizumab in Combination with the Oncolytic Virus Pelareorep and Chemotherapy in Patients with Advanced Pancreatic Adenocarcinoma: A Phase Ib Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Type I interferon signaling, regulation and gene stimulation in chronic virus infection.Seminars in immunology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
CD8 T cells are necessary for the elimination of intracellular pathogens, but during chronic viral infections, CD8 T cells become exhausted and unable to control the persistent infection. Programmed cell death-1 (PD-1) blockade therapies have been shown to improve CD8 T cell responses during chronic viral infections. These therapies have been licensed to treat cancers in humans, but they have not yet been licensed to treat chronic viral infections because limited benefit is seen in pre-clinical animal models of chronic infection. In the present study, we investigated whether TLR4 triggering could improve PD-1 therapy during a chronic viral infection. Using the model of chronic lymphocytic choriomeningitis virus (LCMV) infection in mice, we show that TLR4 triggering with sublethal doses of lipopolysaccharide (LPS) followed by PD-1 blockade results in superior improvement in circulating virus-specific CD8 T cell responses, relative to PD-1 blockade alone. Moreover, we show that the synergy between LPS and PD-1 blockade is dependent on B7 costimulation and mediated by a dendritic cell (DC) intrinsic mechanism. Systemic LPS administration may have safety concerns, motivating us to devise a safer regimen. We show that ex vivo activation of DCs with LPS, followed by adoptive DC transfer, results in a similar potentiation of PD-1 therapy without inducing wasting disease. In summary, our data demonstrate a previously unidentified role for LPS/TLR4 signaling in modulating the host response to PD-1 therapy. These findings may be important for developing novel checkpoint therapies against chronic viral infection.
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