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.

原理：组蛋白macroH2A1的丢失会诱导肝细胞癌（HCC）中的癌干细胞（CSCs）样细胞的出现。CSC如何与肿瘤微环境和适应性免疫系统相互作用尚不清楚。

方法：我们筛选了侵袭性人类HCC中的macroH2A1和CD44 CSC标志物表达。我们还敲低了肝癌细胞中的（KD）macroH2A1，并进行了整合的转录组和分泌组分析。

结果：与对照组织相比，人类HCC显示出低macroH2A1和高CD44表达。MacroH2A1 KD CSC样细胞将其化学抗性从旁环转移到亲本HCC细胞。MacroH2A1 KD条件培养基经转录重新编程的HCC亲本细胞激活了调节性CD4 ⁺ / CD25 ⁺ / FoxP3 ⁺ T细胞（Tregs）。

结论： HCC细胞中macroH2A1的丢失驱动了癌症干细胞的增殖和逃避免疫监测。