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| Status |
Public on Sep 24, 2024 |
| Title |
Neoadjuvant anti-PD1 immunotherapy for surgically accessible recurrent glioblastoma: clinical and molecular outcomes of a stage 2 single-arm expansion cohort |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Glioblastoma is immunologically “cold” and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we performed bulk-RNA seq on resected tumor tissue in an additional 25 patients with surgically-accessible recurrent glioblastoma. Neoadjuvant pembrolizumab was associated with suppression of cell cycle/cancer proliferation genes and upregulation of T-cell/interferon-related gene expression. This signature was unique to patients treated with neoadjuvant pembrolizumab and was an independent risk factor for survival. Our results demonstrate a clear pharmacodynamic effect of anti-PD1 therapy in glioblastoma and identify pathways that may mediate resistance. However, we did not confirm a survival benefit to neoadjuvant pembrolizumab in recurrent glioblastoma. Our new data suggests some patients may exhibit innate resistance to pre-surgical ICI and require other concomitant therapies to sensitize effectively.
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| Overall design |
Total RNA was extracted from the resected tumor specimens of patients enrolled in the neoadjuvant expansion cohort who received pembrolizumab. The extracted RNA was then sent for RNA sequencing.
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| Contributor(s) |
McFaline-Figueroa JR, Sun L, Qiao Y, Youssef GC, Li G, Kim J, Lee E, Nayak L, Chukwueke U, Beroukhim R, Batchelor T, Chiocca EA, Doherty L, Stefanik J, Partridge K, Spearman A, Myers A, Westergaard C, Russ A, Lavallee M, Smokovich A, LaForest-Roys C, Fox Garcia R, McCluskey C, Bi WL, Arnaout O, Peruzzi P, Cosgrove GR, Ligon KL, Arrillaga-Romany I, Clarke JL, Reardon DA, Cloughesy TF, Prins RM, Wen PY |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Apr 23, 2024 |
| Last update date |
Sep 24, 2024 |
| Contact name |
Lu Sun |
| Organization name |
University of California, LA
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| Street address |
10833 Le Conte Avenue
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| City |
Los Angeles |
| State/province |
California |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (20)
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| GSM8226255 |
Patient 38, extension |
| GSM8226256 |
Patient 40, extension |
| GSM8226257 |
Patient 41, extension |
| GSM8226258 |
Patient 42, extension |
| GSM8226259 |
Patient 44, extension |
| GSM8226260 |
Patient 46, extension |
| GSM8226261 |
Patient 47, extension |
| GSM8226262 |
Patient 48, extension |
| GSM8226263 |
Patient 49, extension |
| GSM8226264 |
Patient 50, extension |
| GSM8226265 |
Patient 51, extension |
| GSM8226266 |
Patient 52, extension |
| GSM8226267 |
Patient 54, extension |
| GSM8226268 |
Patient 55, extension |
| GSM8226269 |
Patient 56, extension |
| GSM8226270 |
Patient 58, extension |
| GSM8226271 |
Patient 59, extension |
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| Relations |
| BioProject |
PRJNA1103815 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE264695_Prins.PD1NeoAdjv.Combo.Merck.Nov2022.htseqCount.SampleRenamedForGEO.xlsx |
3.8 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
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