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| Status |
Public on Jan 01, 2023 |
| Title |
Losartan controls immune checkpoint blocker-induced edema and improves survival in glioblastoma |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Immune checkpoint blockers (ICBs) have failed in all Phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema in some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, and T cell blocking studies in mice, we demonstrated that this edema results from an inflammatory response following anti-PD1 antibody treatment that disrupts the blood-tumor-barrier. Used in lieu of immunosuppressive corticosteroids, the angiotensin receptor blocker losartan prevented this ICB-induced edema and reprogrammed the tumor microenvironment, curing 20% of mice which increased to 40% in combination with standard of care treatment. Using a bihemispheric tumor model, we identified a “hot” tumor immune signature prior to losartan+anti-PD1 therapy that predicted long-term survival. Our findings provide the rationale and associated biomarkers to test losartan with ICBs in glioblastoma patients.
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| Overall design |
single-cell RNA-seq
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| Contributor(s) |
Datta M, Chatterjee S, Perez EM, Gritsch S, Roberge S, Duquette M, Chen IX, Naxerova K, Kumar AS, Ghosh M, Emblem KE, Ng MR, Ho WW, Kumar P, Krishnan S, Dong X, Speranza MC, Neagu MR, Reardon DA, Sharpe AH, Freeman GJ, Suvà ML, Xu L, Jain RK |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Aug 29, 2022 |
| Last update date |
Jan 01, 2023 |
| Contact name |
Elizabeth Perez |
| Organization name |
MGH
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| Street address |
30 Fruit Street
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02114 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (1078)
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| Relations |
| BioProject |
PRJNA874707 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE212246_TPM_qc.csv.gz |
11.1 Mb |
(ftp)(http) |
CSV |
| GSE212246_metadata_mGBM.csv.gz |
14.9 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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