Omics · study · 2026
A Glutamine Antagonist Prodrug Reprograms Dendritic Cells to Enhance Colorectal Cancer Immunotherapy
Listed in NCBI GEO
The tumor microenvironment (TME) imposes profound metabolic and immunosuppressive barriers that compromise the functionality of immune cells and limit effective anti-tumor responses.
Description
A hallmark of many tumors is their heightened dependency on glutamine as a metabolic substrate, which leads to glutamine depletion within the TME. This glutamine scarcity impairs the function of dendritic cells (DCs), resulting in defective antigen presentation and diminished activation of CD8⁺ cytotoxic T cells.
Here, we report T26, a bifunctional immunometabolic prodrug composed of JHU083 (a glutamine antagonist) and MSA-2 (a STING agonist), designed to restore DC functionality and enhance anti-tumor immunity. T26 effectively suppresses tumor growth in colorectal cancer (CRC) models by reprogramming the TME toward a more immunostimulatory state. Mechanistically, T26 promotes DC maturation, enhances antigen presentation, and facilitates robust CD8⁺ T cell responses, leading to durable tumor suppression.
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Importantly, DC depletion experiments demonstrate that the anti-tumor efficacy of T26 is critically dependent on DC activation. Moreover, T26 reprograms tumor-derived extracellular vesicles (EVs), enhancing their capacity to transmit immunostimulatory signals and support CD8⁺ T cell–mediated cytotoxicity. In addition, T26 exhibits strong synergistic effects when combined with standard chemotherapy, immune checkpoint blockade, and anti-angiogenic therapy, further potentiating therapeutic efficacy.
Collectively, these findings position T26 as a promising candidate for combination cancer immunotherapy, offering a dual-acting strategy that overcomes metabolic suppression and immune evasion in the TME to improve treatment outcomes.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296658 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296658 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1260465 ncbi.nlm.nih.gov/bioproject/PRJNA1260465 ↗
project · from NCBI GEO
- PubMed 41173791 pubmed.ncbi.nlm.nih.gov/41173791 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE296658 | 15 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 (75%) |
| 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:10090 | 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 |