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| 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
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| 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.
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| 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.
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| Contributor(s) |
Wisdom AJ, Mowery YM, Kirsch DG, Zhang D, Qin X, Owzar K |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| 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 |
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| Submission date |
Jul 15, 2019 |
| Last update date |
Apr 28, 2020 |
| Contact name |
David Kirsch |
| E-mail(s) |
david.kirsch@duke.edu
|
| Organization name |
Duke University
|
| Street address |
PO Box 96100
|
| City |
Durham |
| State/province |
NC |
| ZIP/Postal code |
27710 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (48)
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| Relations |
| BioProject |
PRJNA554626 |
| SRA |
SRP214609 |
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