Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation
- Autori: Lo Re O.; Mazza T.; Giallongo S.; Sanna P.; Rappa F.; Vinh Luong T.; Li Volti G.; Drovakova A.; Roskams T.; Van Haele M.; Tsochatzis E.; Vinciguerra M.
- Anno di pubblicazione: 2020
- Tipologia: Articolo in rivista
- Parole Chiave: adaptive immune system; chemoresistance.; hepatocellular carcinoma; histone macroH2A1
- OA Link: http://hdl.handle.net/10447/392894
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.