Bhat, Jaydeep and Dubin, Samuel and Dananberg, Alexandra and Quabius, Eiger Susanne and Fritsch, Juergen and Dowds, C. Marie and Saxena, Ankit and Chitadze, Guranda and Lettau, Marcus and Kabelitz, Dieter (2019) Histone Deacetylase Inhibitor Modulates NKG2D Receptor Expression and Memory Phenotype of Human Gamma/Delta T Cells Upon Interaction With Tumor Cells. FRONTIERS IN IMMUNOLOGY, 10: 569. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
The functional plasticity and anti-tumor potential of human gamma delta T cells have been widely studied. However, the epigenetic regulation of gamma delta T-cell/tumor cell interactions has been poorly investigated. In the present study, we show that treatment with the histone deacetylase inhibitor Valproic acid (VPA) significantly enhanced the expression and/or release of the NKG2D ligands MICA, MICB and ULBP-2, but not ULBP-1 in the pancreatic carcinoma cell line Panc89 and the prostate carcinoma cell line PC-3. Under in vitro tumor co-culture conditions, the expression of full length and the truncated form of the NKG2D receptor in gamma delta T cells was significantly downregulated. Furthermore, using a newly established flow cytometry-based method to analyze histone acetylation (H3K9ac) in gamma delta T cells, we showed constitutive H3K9ac(low) and inducible H3K9ac(high) expression in V delta 2 T cells. The detailed analysis of H3K9ac(low) V delta 2 T cells revealed a significant reversion of T-EMRA to T-EM phenotype during in vitro co-culture with pancreatic ductal adenocarcinoma cells. Our study uncovers novel mechanisms of how epigenetic modifiers modulate gamma delta T-cell differentiation during interaction with tumor cells. This information is important when considering combination therapy of VPA with the gamma delta T-cell-based immunotherapy for the treatment of certain types of cancer.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENE-EXPRESSION; VALPROIC ACID; MEDIATED LYSIS; LIGANDS; CANCER; DIFFERENTIATION; ACTIVATION; INVOLVEMENT; DISINTEGRIN; MECHANISM; gamma/delta T cells; HDAC inhibitor(s); histone acetylation; NKG2D; memory T cells; tumor microenvironment; valproic acid |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Apr 2020 10:12 |
| Last Modified: | 15 Apr 2020 10:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27333 |
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