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| Status |
Public on May 04, 2022 |
| Title |
Small extracellular vesicles induce resistance to anti-GD2 immunotherapy unveiling tipifarnib as an adjunct to neuroblastoma immunotherapy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
We utilize the syngeneic 9464D-GD2 mouse model to investigate the role of neuroblastoma-derived small extracellular vesicles (sEVs) in developing resistance to the anti-GD2 monoclonal antibody dinutuximab. RNA-sequencing and flow cytometry analysis of whole tumors revealed that neuroblastoma-derived sEVs modulate immune cell tumor infiltration upon dinutuximab treatment to create an immunosuppressive tumor microenvironment that contains more tumor-associated macrophages (TAMs) and fewer tumor-infiltrating NK cells. Importantly, tipifarnib, a farnesyltransferase inhibitor that inhibits sEV secretion, drastically enhanced the efficacy of dinutuximab and reversed the immunosuppressive effects of neuroblastoma-derived sEVs.
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| |
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| Overall design |
We performed RNA-seq after isolated subcutaneous tumors from female mice receiving 5 treatments of dinutuximab or dinutuximab plus sEVs derived from 9464D-GD2 cells. Each treatment group contains two biological replicates.
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| |
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| Contributor(s) |
Liu X, Wang H |
| Citation(s) |
35483745 |
| |
| Submission date |
Nov 30, 2021 |
| Last update date |
May 05, 2022 |
| Contact name |
Hong-Gang Wang |
| E-mail(s) |
hwang3@pennstatehealth.psu.edu
|
| Organization name |
Penn State College of Medicine
|
| Department |
Pediatrics
|
| Lab |
Hong-Gang Wang
|
| Street address |
500 University Drive, H085, Rm C7833B
|
| City |
Hershey |
| State/province |
PA |
| ZIP/Postal code |
17033 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (4)
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| Relations |
| BioProject |
PRJNA785155 |
| SRA |
SRP348998 |
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