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Series GSE134273 Query DataSets for GSE134273
Status Public on Mar 10, 2020
Title A single cell atlas of tumor resistance to PD-1 blockade and radiotherapy: Bulk Tumor RNA Sequencing
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Abstract: Transplanted tumors in syngeneic mice treated with immune checkpoint blockade and radiotherapy demonstrate synergy and an abscopal effect. Indeed, tumors generated from sarcoma cell lines transplanted into syngeneic mice are cured by PD-1 blockade and radiotherapy, but autochthonous, primary sarcomas from the same high mutational load model are resistant to the identical treatment. Here, we generated a single cell atlas of tumor-infiltrating immune cells from allograft and primary tumors, which demonstrates marked differences in their immune landscapes before and after radiation and immunotherapy. Allograft tumors are enriched for effector CD8+ T cells that mediate response to combination therapy, but the immune response to primary sarcomas shows tumor-specific tolerance. Genetic barcoding of primary tumors reveals a cellular response to combination therapy, but resistance of specific clones. Together, this comprehensive comparison of the primary and allograft tumor microenvironments identifies immune tolerance and clonal resistance to immunotherapy and radiotherapy specific to primary tumors.
Overall design Primary and allograft sarcomas were harvested 3 days after treatment with either 0 or 20 Gy radiation and anti-PD-1 or isotype control treatment.
Contributor(s) Wisdom AJ, Mowery YM, Kirsch DG, Zhang D, Qin X, Owzar K
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NIH grant(s)
Grant ID Grant title Affiliation Name
R35 CA197616 Advancing Cancer Therapy through Ground Breaking Research in Radiation Biology DUKE UNIVERSITY David Guy Kirsch
F30 CA221268 Dissecting the role of the immune system in the radiation response of Kras-mutant tumors DUKE UNIVERSITY Amy Jordan Wisdom
Submission date Jul 15, 2019
Last update date Apr 28, 2020
Contact name David Kirsch
Organization name Duke University
Street address PO Box 96100
City Durham
State/province NC
ZIP/Postal code 27710
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (48)
GSM3941263 A0I-500595-T-RNA [S97]
GSM3941264 A0I-500545-T-RNA [S98]
GSM3941265 A0I-500551-T-RNA [S99]
BioProject PRJNA554626
SRA SRP214609

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Supplementary file Size Download File type/resource
GSE134273_rnaseq-expression_counts_1strun.csv.gz 2.0 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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