Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation

Francesca Rappa, Emmanuel Tsochatzis, Tu Vinh Luong, Oriana Lo Re, Matthias Van Haele, Sebastiano Giallongo, Giovanni Li Volti, Adela Drovakova, Paola Sanna, Manlio Vinciguerra, Giovanni Li Volti, Tania Roskams, Tommaso Mazza

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)910-924
Number of pages15
JournalTheranostics
Volume10
Publication statusPublished - 2020

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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