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Series GSE121810 Query DataSets for GSE121810
Status Public on Dec 05, 2018
Title Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Glioblastoma is the most common primary malignant brain tumor in adults and associated with poor survival. Standard-of-care chemotherapy and radiation confer a median overall survival of under two years. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab, a programmed cell death protein 1 (PD-1) monoclonal antibody, in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical PD-1 blockade alone (hazard ratio = 0.39; P = 0.04, log-rank test). Neoadjuvant PD-1 blockade was associated with upregulation of T cell and interferon-γ-related genes, but downregulation of cell cycle related genes within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 (PD-L1) in the tumor microenvironment was observed more frequently in the neoadjuvant group than in tumors obtained from patients treated only in the adjuvant setting. Similarly, neoadjuvant pembrolizumab was associated with clonal T cell expansion and the overlap of T cell receptors between tumor and blood, decreased PD-1 expression in T cells and a decreasing peripheral monocytic population. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances the local and systemic anti-tumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor. This trial was registered with under the identifier NCT02852655 (
Overall design This dataset contains the transcriptomes of recurrent glioblastoma with either neoadjuvant (1 dose) or adjuvant pembrolizumab treatment
Contributor(s) Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, Wang AC, Ellingson BM, Rytlewski JA, Sanders CM, Kawaguchi ES, Du L, Li G, Yong WH, Gaffey SC, Cohen AL, Mellinghoff IK, Lee EQ, Reardon DA, O’Brien BJ, Butowski NA, Nghiemphu PL, Clarke JL, Arrillaga-Romany IC, Colman H, Kaley TJ, de Groot JF, Liau LM, Wen PY, Prins RM
Citation(s) 30742122
Submission date Oct 25, 2018
Last update date Feb 13, 2019
Contact name Willy Hugo
Organization name UCLA
Department Medicine
Street address 10833 Le Conte Ave, 52-121 CHS, Division of Dermatology
City Los Angeles
State/province California
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (29)
GSM3447008 Patient 3 tumor
GSM3447009 Patient 4 tumor
GSM3447010 Patient 5 tumor
BioProject PRJNA498500
SRA SRP166889

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Supplementary file Size Download File type/resource
GSE121810_Prins.PD1NeoAdjv.Jul2018.HUGO.PtID.xlsx 5.3 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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