Evidence mapPaperPMID 38869480Full record

ArticleThe Journal of experimental medicine2024

PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway.

Jonathan J Hodgins, John Abou-Hamad, Colin Edward O'Dwyer, Ash Hagerman, Edward Yakubovich, Christiano Tanese de Souza, Marie Marotel, Ariel Buchler, Saleh Fadel, Maria M Park and 16 more

Abstract read
In one paragraph

Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
field-weighted citation impact
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

12 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Breaking Immunosuppression to Enhance Cancer Stem Cell-Targeted Immunotherapy.International journal of biological sciences · 2025
    Review
  9. Review
  10. Review
  11. Article
  12. Article
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

26 authors.

Jonathan J HodginsCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0002-0390-5599
John Abou-HamadCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0009-0004-9407-9043
Colin Edward O'DwyerCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0009-0004-9615-6209
Ash HagermanCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0001-8417-7409
Edward YakubovichCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0002-2109-1111
Christiano Tanese de SouzaCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0003-2982-8795
Marie MarotelCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0002-1618-7602
Ariel BuchlerDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada.ORCID 0000-0002-4016-032X
Saleh FadelThe Ottawa Hospital , Ottawa, Canada.ORCID 0000-0002-1546-5324
Maria M ParkCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0009-0008-7847-144X
Claire Fong-McMasterDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada.ORCID 0009-0007-5713-5386
Mathieu F CrupiCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0002-4452-2383
Olivia Joan MakinsonCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0002-4570-8534
Reem KurdiehCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0009-0000-5069-9436
Reza RezaeiCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0001-9652-9328
Harkirat Singh DhillonCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0009-0003-4613-520X
Carolina S IlkowCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0003-3488-4062
John C BellCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0002-9083-357X
Mary-Ellen HarperDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada.ORCID 0000-0003-3864-5886
Benjamin H RotsteinDepartment of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada.ORCID 0000-0001-9707-9357
Rebecca C AuerCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0002-3617-0015
Barbara C VanderhydenCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0002-7644-7189
Luc A SabourinCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0002-1593-0978
Marie-Claude Bourgeois-DaigneaultDepartment of Microbiology, Infectious Diseases, and Immunology, University of Montreal, Montreal, Canada.ORCID 0000-0002-9091-2235
David P CookCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0001-7639-6724
Michele ArdolinoCancer Therapeutics Program, Ottawa Hospital Research Institute , Ottawa, Canada.ORCID 0000-0003-4114-0985

Funding

BioCanRxCanadian Allergy, Asthma, and Immunology FoundationCanadian Cancer Society Research InstituteCanadian Fund for InnovationCancer Research SocietyCharles Best Canada Graduate Scholarships DoctoralCI3 scholarshipCIHRNatural Sciences and Engineering Research Council of CanadaOntario Graduate ScholarshipProstate Cancer CanadaRide for DadSchulich Leader ScholarshipTaggart-Parkes FellowshipTerry Fox FoundationTerry Fox Research InstituteUniversity of OttawaUniversity of Ottawa Heart InstituteVanier Canada
6 · The paper itself

Abstract

While conventional wisdom initially postulated that PD-L1 serves as the inert ligand for PD-1, an emerging body of literature suggests that PD-L1 has cell-intrinsic functions in immune and cancer cells. In line with these studies, here we show that engagement of PD-L1 via cellular ligands or agonistic antibodies, including those used in the clinic, potently inhibits the type I interferon pathway in cancer cells. Hampered type I interferon responses in PD-L1-expressing cancer cells resulted in enhanced efficacy of oncolytic viruses in vitro and in vivo. Consistently, PD-L1 expression marked tumor explants from cancer patients that were best infected by oncolytic viruses. Mechanistically, PD-L1 promoted a metabolic shift characterized by enhanced glycolysis rate that resulted in increased lactate production. In turn, lactate inhibited type I IFN responses. In addition to adding mechanistic insight into PD-L1 intrinsic function, our results will also help guide the numerous ongoing efforts to combine PD-L1 antibodies with oncolytic virotherapy in clinical trials.

Indexed as

B7-H1 AntigenInterferon Type IOncolytic VirotherapyOncolytic VirusesAnimalsCell Line, TumorFemaleGlycolysisHumansLactic AcidMaleMiceNeoplasmsSignal TransductionB7-H1 AntigenCD274 protein, humanInterferon Type ILactic Acid

Identifiers

PMID38869480
PMCPMC11176258

What Socratic holds

Textmetadata
LicenceCC BY-NC-SA
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 Socratic graph.