Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4(+)CD25(+)FoxP3(+) regulatory T cells activation
| Authors | |
|---|---|
| Year of publication | 2020 |
| Type | Article in Periodical |
| Magazine / Source | THERANOSTICS |
| MU Faculty or unit | |
| Citation | |
| web | https://www.thno.org/v10p0910.htm |
| Doi | http://dx.doi.org/10.7150/thno.35045 |
| Keywords | hepatocellular carcinoma; histone macroH2A1; adaptive immune system; chemoresistance |
| Description | Rationale: Loss of histone macroH2A1 induces appearance of cancer stem cells (CSCs)-like cells in hepatocellular carcinoma (HCC). How CSCs interact with the tumor microenvironment and the adaptive immune system is unclear. Methods: We screened aggressive human HCC for macroH2A1 and CD44 CSC marker expression. We also knocked down (KD) macroH2A1 in HCC cells, and performed integrated transcriptomic and secretomic analyses. Results: Human HCC showed low macroH2A1 and high CD44 expression compared to control tissues. MacroH2A1 KD CSC-like cells transferred paracrinally their chemoresistant properties to parental HCC cells. MacroH2A1 KD conditioned media transcriptionally reprogrammed parental HCC cells activated regulatory CD4(+)/CD25(+)/FoxP3(+) T cells (Tregs). Conclusions: Loss of macroH2A1 in HCC cells drives cancer stem-cell propagation and evasion from immune surveillance. |
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