Journal article
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 methylation inversely correlates with transcription, protein level, and cytotoxicity. Altogether, we propose that a sizeable portion of human tumor-specific CTLs are deficient in IFNγ response, contributed by CpG hypermethylation of the IFNγ promoter. Our findings have important implications for immunotherapy strategies and for methods to detect human antigen-specific T cells.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.4MB, Terms of use)
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- Publisher copy:
- 10.3389/fimmu.2020.00310
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Immunology More from this journal
- Volume:
- 11
- Article number:
- 310
- Publication date:
- 2020-03-05
- Acceptance date:
- 2020-02-07
- DOI:
- EISSN:
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1664-3224
- Language:
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English
- Keywords:
- Pubs id:
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1091113
- Local pid:
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pubs:1091113
- Deposit date:
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2020-03-05
- ARK identifier:
Terms of use
- Copyright holder:
- Abd Hamid, M et al.
- Copyright date:
- 2020
- Rights statement:
- © 2020 Abd Hamid, Yao, Waugh, Rosendo-Machado, Li, Rostron, Frankland, Peng and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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