Omics · study · 2026
A metabolic switch that boosts immune cell fitness against cancer [Bulk RNA-seq]
Listed in NCBI GEO
Cell competition, which prunes less fit cells to ensure tissue stability, is exploited by cancer to dampen immune surveillance.
Description
Despite the success of immunotherapy in a subset of cancer patients, the determinants of immune fitness in the tumor microenvironment, critical to enhancing immunotherapy, remain poorly understood. Here, we identify the lipid-sensing transcription factor PPAR as an immune-intrinsic switch that boosts the fitness of anti-tumor immunity and eliminates cancer irrespective of antigenicity, immune infiltration status, stage or type without any adverse effects.
Among tumor-infiltrating immune cells that exhibit elevation of fitness, CD8+ T cells are necessary and sufficient in driving PPAR-induced boost in anti-tumor immunity. Mechanistically, PPARδ activation in CD8 T cells evokes metabolic reprogramming to increase nucleotide synthesis and fatty acid oxidation. Ablation of Cpt1a, the rate limiting enzyme of fatty acid oxidation, blunts the fitness of CD8+ T cells and reduces the effects of PPARδ on anti-tumor immunity.
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Therapeutically, activation of PPARδ in CD8+ T cells facilitates the eradication of established microsatellite stable metastatic colorectal cancer by checkpoint blockade immunotherapy in mice. Finally, human CAR-T cells with active PPARδ are superior in controlling tumor growth ex vivo. Our findings define PPARδ – Cpt1a axis as a metabolic determinant of immune fitness against cancer, which can be harnessed to improve therapeutic outcomes in tumors that are resistant to current modes of immunotherapy.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE248nnn/GSE248000 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE248000 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1041386 ncbi.nlm.nih.gov/bioproject/PRJNA1041386 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Biochemistry and cell biology 68% · Cancer 75% · RNA sequencing 65%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE248000 | 12 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].anzsrc:group:3101 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (68%) |
| 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| 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 |