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Series GSE124620 Query DataSets for GSE124620
Status Public on Feb 13, 2019
Title Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Improvements in cancer immunotherapy are needed. The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors. Peptide mimics a viral reinfection event to memory CD8+ T cells, triggering antigen presentation and cytotoxic pathways within the tumor, activating dendritic cells and natural killer cells, and recruiting the adaptive immune sytem. Viral peptide treatment of ex vivo human tumors recapitulates immune activation gene expression profiles in mice. Lastly, peptide therapy renders resistant mouse tumors susceptible to PD-L1 blockade. Thus, re-stimulating known antiviral immunity may provide a unique therapeutic approach for cancer immunotherapy.
Overall design For B16 mouse tumor studies, B16 tumors in OT-1 chimeras were treated with relevant or irrelevant viral peptide. 9 hours after peptide delivery, B16 tumors were harvested from 3 mice per group. RNA was isolated from tumor homogenate for sequencing.
For Braf/Pten tumor studies, murine melanoma tumors in OT-1 chimeras were isolated, sliced into thin sections, and incubated with relevant or irrelevant peptide ex vivo. RNA was isolated from tumor culture homogenate for sequencing.
For human tumor samples, tumors were sliced into thin sections, and incubated with relevant or irrelevant viral peptides ex vivo. RNA was isolated from tumor culture homogenate for sequencing.
Contributor(s) Rosato PC, Wijeyesinghe S, Masopust D
Citation(s) 30718505
Submission date Jan 03, 2019
Last update date Mar 27, 2019
Contact name Sathi Wijeyesinghe
Organization name University of Minnesota
Street address 2101 6TH ST SE, RM 2-142
City Minneapolis
State/province MN
ZIP/Postal code 55455
Country USA
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (34)
GSM3538008 B16 control1
GSM3538009 B16 control2
GSM3538010 B16 control3
BioProject PRJNA512856
SRA SRP175164

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Supplementary file Size Download File type/resource
GSE124620_B16_Normalized_Counts_with_Annotation.csv.gz 1.5 Mb (ftp)(http) CSV
GSE124620_B16_Unnormalized_Counts.csv.gz 387.6 Kb (ftp)(http) CSV
GSE124620_Human1_Normalized_Counts_with_Annotation.csv.gz 1.4 Mb (ftp)(http) CSV
GSE124620_Human1_Unnormalized_Counts.csv.gz 444.3 Kb (ftp)(http) CSV
GSE124620_Human2_Normalized_Counts_with_Annotation.csv.gz 3.8 Mb (ftp)(http) CSV
GSE124620_Human2_Unnormalized_Counts.csv.gz 973.4 Kb (ftp)(http) CSV
GSE124620_Ptenbraf_ReSeq_Unnormalized_Counts.csv.gz 365.4 Kb (ftp)(http) CSV
GSE124620_Ptenbraf_Reseq_Normalized_Counts_with_Annotation.csv.gz 1.2 Mb (ftp)(http) CSV
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