Transcriptomics

Dataset Information

0

Suppression of antitumor immunity by the oncometabolite 2-hydroxyglutarate


ABSTRACT: Isocitrate dehydrogenase (IDH) mutations, a hallmark of gliomagenesis, result in the production of the oncometabolite R-2-hydroxyglutarate (R-2-HG) which is thought to promote tumorigenesis via DNA methylation. Here we identify an additional immunosuppressive activity of R-2-HG: Tumor cell-derived R-2-HG is taken up by T-cells where it induces a strong and immediate perturbation of calcium- and ATP-dependent signaling events, and polyamine biosynthesis. This results in a profound suppression of antigen-specific T-cell activation and effector cytokine production in experimental mouse and human systems. In a large cohort of WHO grade II and III gliomas, IDH1 mutant tumors display reduced infiltration by T-cells compared to IDH1 wildtype tumors. Spontaneous and induced mutation-specific antitumor immunity to syngeneic IDH1-mutant tumors in MHC-humanized mice is improved by isolated genetic ablation of the neomorphic enzymatic function of mutant IDH1. Taken together, these data attribute a novel, fundamentally non-tumor-cell-autonomous role of an oncometabolite in shaping the tumor immune microenvironment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84849 | GEO | 2016/07/27

SECONDARY ACCESSION(S): PRJNA335373

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2016-07-27 | E-GEOD-84849 | biostudies-arrayexpress
2012-10-25 | E-GEOD-41802 | biostudies-arrayexpress
2012-10-25 | GSE41802 | GEO
2023-04-15 | E-MTAB-11328 | biostudies-arrayexpress
| EGAS00001001854 | EGA
2018-06-01 | GSE103556 | GEO
2018-06-01 | GSE103557 | GEO
2024-08-10 | PXD022137 | Pride
2024-04-24 | GSE265829 | GEO
2024-04-24 | GSE265788 | GEO