Defective Interferon Gamma Production by Tumor-Specific CD8⁺ T Cells Is Associated With 5'Methylcytosine-Guanine Hypermethylation of Interferon Gamma Promoter.

ABSTRACT: Interferon gamma (IFNγ) supports effector responses of CD8⁺ cytotoxic T lymphocytes (CTLs) and is a surrogate marker for detection of antigen-specific T cells. Here, we show that tumor-specific CTL clones have impaired IFNγ expression and production upon activation. Assessment of the relationship between IFNγ production and the 5'methylcytosine-guanine (CpG) dinucleotide methylation of the IFNγ promoter using bisulfite treatment has shown that IFNγ^- CTL clones accumulates CpG hypermethylation within the promoter at key transcription factor binding sites (-186 and -54), known to be vital for transcription. We confirmed these findings using ex vivo isolated and short-term expanded bulk tumor-specific CTL lines from four cancer patients and demonstrated that IFNγ

SUBMITTER: Abd Hamid M 

PROVIDER: S-EPMC7066077 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature