| Accession |
PRJCA048032 |
| Title |
Single-cell transcriptome atlas reveals the underlying mechanism of kynurenic acid in the regulation of tumor immune microenvironment in glioblastoma |
| Relevance |
Model organism |
| Data types |
Single cell sequencing
|
| Organisms |
Mus musculus
|
| Description |
Tryptophan metabolism plays a critical role in glioblastoma (GBM), but the regulatory functions of kynurenic acid (KYNA) in this context remain unclear. Using an orthotopic GBM mouse model treated with KYNA, we employed multi-omics analysis (scRNAseq, CyTOF, proteomics) to profile changes in the tumor immune microenvironment (TIME). KYNA treatment significantly reduced tumor burden in GBM-bearing WT mice. CyTOF analysis indicated enhanced effector functions in T lymphocytes upon KYNA treatment, while scRNA-seq revealed shifts in T cell phenotypic diversity within the GBM TIME. Crucially, this anti-tumor effect was abrogated in T cell-deficient mouse models (nude and Rag2-/-), demonstrating its dependence on adaptive immunity. Proteomic analyses and in vitro experiments demonstrated that KYNA treatment was associated with reduced markers of CD8+ T cell exhaustion and concomitant promotion of cytotoxic activation. Collectively, these data suggest that KYNA modulates the GBM TIME, correlating with inhibition of T cell exhaustion signatures and enhancement of CD8+ T cell activation and cytotoxic potential. This modulation is contingent upon the presence of functional T cells. This study provides novel insights into KYNA's role in GBM, highlighting its association with altered T cell diversity and function within the brain tumor microenvironment. |
| Sample scope |
Single cell |
| Release date |
2025-10-15 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 41221633
|
Single‐Cell Transcriptome Atlas Reveals the Underlying Mechanism of Kynurenic Acid in the Regulation of Tumor Immune Microenvironment in Glioblastoma
|
Advanced Science
|
10.1002/advs.202507705
|
2025
|
|
|
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| National Natural Science Foundation of China (NSFC)
|
|
82472069
|
|
| National Natural Science Foundation of China (NSFC)
|
|
92253304
|
|
|
|
| Submitter |
liming
sun (sunlm@ucas.ac.cn)
|
| Organization |
Shanghai Institute of Biochemistry and Cell Biology, CAS |
| Submission date |
2025-10-13 |
