Omics · study · 2026
Complement Protease C1s Drives Immunosuppression in Mesenchymal Glioblastoma by Rewiring Microglia Metabolism
Listed in NCBI GEO
The mesenchymal (MES) subtype of glioblastoma (GBM) exhibits a highly immunosuppressive tumor microenvironment (TME) and poor prognosis, but the underlying mechanism remains largely unclear.
Description
Herein, we demonstrate that the MES-GBM cells-derived complement protease C1s plays a crucial role in suppressing anti-tumor immunity and fostering resistance to immunotherapy in GBM. Complement components C1s and C1r are highly expressed in MES-GBM via the IL-1β/NF-κB signaling pathway.
C1s binds to FGFR1 on microglial cells and cleaves FGF2, thereby inhibiting the FGFR1 pathway. This inhibition promotes mitochondrial oxidative phosphorylation and M2 microglial polarization. Depletion of C1s in MES-GBM cells restores CD8+ T cell anti-tumor immunity and inhibits GBM tumorigenesis.
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Furthermore, the inhibition of C1s with BCX1470 reduces tumor growth and enhances GBM sensitivity to anti-PD-L1 immunotherapy in mice. Therefore, our study reveals the pivotal function of C1s in MES-GBM immunosuppression and immunotherapy resistance, indicating a promising therapeutic target for GBM.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313917 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313917 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1387235 ncbi.nlm.nih.gov/bioproject/PRJNA1387235 ↗
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 | GSE313917 | 13 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 |