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Series GSE210884 Query DataSets for GSE210884
Status Public on Jun 28, 2023
Title More than a ligand: PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I interferon pathway
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Targeting the PD-1/PD-L1 axis has transformed the field of immune-oncology. 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 PD-L1 potently inhibits the type I interferon pathway in cancer cells. Hampered type I interferon responses in PD-L1-expressing cells resulted in enhanced infection with oncolytic viruses in cancer cells in vitro and in vivo. PD-L1 expression marks tumor explants from cancer patients that are best infected by oncolytic viruses. Agonistic antibodies targeting PD-L1 further reduced type I IFN responses and enhanced oncolytic virus infection. Mechanistically, PD-L1 suppressed type I interferon by promoting Warburg metabolism, characterized by enhanced glucose uptake and glycolysis rate. Lactate generated from glycolysis was the key metabolite responsible for inhibiting type I interferon responses and enhancing oncolytic virus infection in PD‑L1‑expressing cells. In addition to adding mechanistic insight into PD-L1 intrinsic function and showing that PD-L1 has a broader impact on immunity and cancer biology besides acting as a ligand for PD-1, our results will also help guide the numerous efforts currently ongoing to combine PD-L1 antibodies with oncolytic virotherapy in clinical trials.
 
Overall design PolyA RNA-seq of wild-type and PD-L1-KO TRAMP2-C2 cells with and without infection with the oncolytic virus VSVdelta51-YFP at an MOI of 0.1 for 8 hours
 
Contributor(s) Cook DP, Hodgins JJ, Ardolino M
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Submission date Aug 09, 2022
Last update date Jun 28, 2023
Contact name David Cook
E-mail(s) David.cook@uottawa.ca
Organization name Ottawa Hospital Research Institute
Department Cancer Therapeutics Program
Street address 501 Smyth Rd
City Ottawa
State/province ON
ZIP/Postal code K1H8L6
Country Canada
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM6439697 PD-L1 wildtype TRAMP-C2 without oncolytic virus infection (rep 1) [Thy1_Mock_1]
GSM6439698 PD-L1 wildtype TRAMP-C2 without oncolytic virus infection (rep 2) [Thy1_Mock_2]
GSM6439699 PD-L1 wildtype TRAMP-C2 without oncolytic virus infection (rep 3) [Thy1_Mock_3]
Relations
BioProject PRJNA868100

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE210884_tpm_all_samples.csv.gz 2.1 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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