Omics · study · 2026
Dual Immune Checkpoint Blockade Induces Distinct Systemic and Intratumoral Immune Activation in Recurrent Glioblastoma
Listed in NCBI GEO
We conducted a surgical window-of-opportunity trial (NCT04606316) in 63 patients with relapsed, resectable glioblastoma.
Description
Participants received either dual PD-1+CTLA-4 immune checkpoint blockade (ICB) with nivolumab+ipilimumab (Arm 1), nivolumab alone (Arm 2), or placebo (Arm 3) before resection. Following surgery, Arms 1 and 3 received dual ICB, while Arm 2 received nivolumab until progression or unacceptable toxicity.
Median overall survival was 402 days (95% CI, 265–543) in patients who received dual ICB and 276 days (95% CI, 166–698) for patients who received nivolumab alone. Dual ICB elicited robust intratumoral and systemic immune activation characterized by the highest tumor-infiltrating lymphocyte (TIL) density and greater interferon-related gene expression in the blood. TIL density strongly correlated with survival outcomes, while tumor mutational burden did not.
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Blood transcriptional profiling revealed that early interferon signature upregulation after neoadjuvant therapy predicted improved survival, whereas sustained elevation during adjuvant treatment correlated with poorer outcomes. Our results demonstrate the clear pharmacodynamic activity of dual ICB in glioblastoma, with survival outcomes comparing favorably to similar studies.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318645 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318645 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1419709 ncbi.nlm.nih.gov/bioproject/PRJNA1419709 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE318645 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |