Lo Re, O;
Mazza, T;
Giallongo, S;
Sanna, P;
Rappa, F;
Tu, VL;
Li Volti, G;
... Vinciguerra, M; + view all
(2020)
Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4⁺ CD25⁺ FoxP3⁺ regulatory T cells activation.
Theranostics
, 10
(2)
pp. 910-924.
10.7150/thno.35045.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4⁺ CD25⁺ FoxP3⁺ regulatory T cells activation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7150/thno.35045 |
| Publisher version: | https://doi.org/10.7150/thno.35045 |
| Language: | English |
| Additional information: | © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | hepatocellular carcinoma, histone macroH2A1, adaptive immune system, chemoresistance |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10088028 |
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