Evidence map›Paper›PMID 24401835›Full record

ArticleGene therapy2014

Interference with PD-L1/PD-1 co-stimulation during antigen presentation enhances the multifunctionality of antigen-specific T cells.

J J Pen, B D Keersmaecker, C Heirman, J Corthals, T Liechtenstein, D Escors, K Thielemans, K Breckpot

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 82 citations in OpenAlex.

  1. Advances inMolecular therapy. Nucleic acids · 2026
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  12. RNA in Cancer Immunotherapy: Unlocking the Potential of the Immune System.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Review
  13. Article
  14. Advances in Development of mRNA-Based Therapeutics.Current topics in microbiology and immunology · 2022
    Article
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  16. Article
  17. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

J J PenLaboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
B D KeersmaeckerLaboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
C HeirmanLaboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
J CorthalsLaboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
T Liechtenstein1] Division of Infection and Immunity, Rayne Institute, University College London, London, UK [2] Navarrabiomed-FMS, Complejo Hospitalario de Navarra, Pamplona, Spain.
D Escors1] Division of Infection and Immunity, Rayne Institute, University College London, London, UK [2] Navarrabiomed-FMS, Complejo Hospitalario de Navarra, Pamplona, Spain.
K ThielemansLaboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
K BreckpotLaboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
Vrije Universiteit Brussel · BEUniversity College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The release of cytokines by T cells strongly defines their functional activity in vivo. The ability to produce multiple cytokines has been associated with beneficial immune responses in cancer and infectious diseases, while their progressive loss is associated with T-cell exhaustion, senescence and anergy. Consequently, strategies that enhance the multifunctional status of T cells are a key for immunotherapy. Dendritic cells (DCs) are professional antigen presenting cells that regulate T-cell functions by providing positive and negative co-stimulatory signals. A key negative regulator of T-cell activity is provided by binding of programmed death-1 (PD-1) receptor on activated T cells, to its ligand PD-L1, expressed on DCs. We investigated the impact of interfering with PD-L1/PD-1 co-stimulation on the multifunctionality of T cells, by expression of the soluble extracellular part of PD-1 (sPD-1) or PD-L1 (sPD-L1) in human monocyte-derived DCs during antigen presentation. Expression, secretion and binding of these soluble molecules after mRNA electroporation were demonstrated. Modification of DCs with sPD-1 or sPD-L1 mRNA resulted in increased levels of the co-stimulatory molecule CD80 and a distinct cytokine profile, characterized by the secretion of IL-10 and TNF-α, respectively. Co-expression in DCs of sPD-1 and sPD-L1 with influenza virus nuclear protein 1 (Flu NP1) stimulated Flu NP1 memory T cells, with a significantly higher number of multifunctional T cells and increased cytokine secretion, while it did not induce regulatory T cells. These data provide a rationale for the inclusion of interfering sPD-1 or sPD-L1 in DC-based immunotherapeutic strategies.

Indexed as

Antigen PresentationB7-1 AntigenB7 AntigensDendritic CellsHEK293 CellsHumansInterleukin-10Nucleocapsid ProteinsNucleoproteinsProgrammed Cell Death 1 ReceptorRNA, MessengerT-LymphocytesTumor Necrosis Factor-alphaViral ProteinsB7-1 AntigenB7 Antigenshuman parainfluenza virus type 1 nucleoproteinInterleukin-10Nucleocapsid ProteinsNucleoproteinsProgrammed Cell Death 1 ReceptorRNA, MessengerTumor Necrosis Factor-alphaViral Proteins

Identifiers

PMID24401835
OpenAlexW2064358249

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.