6533b834fe1ef96bd129dc68

RESEARCH PRODUCT

Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4

Lo Re OrianaMazza TommasoGiallongo SebastianoSanna PaolaRappa FrancescaVinh Luong TuLi Volti GiovanniDrovakova AdelaRoskams TaniaVan Haele MatthiasTsochatzis EmmanuelVinciguerra Manlio

subject

MaleCarcinoma HepatocellularT-Lymphocytes RegulatoryHistonesadaptive immune systemCell Line TumorParacrine CommunicationTumor MicroenvironmentHumansMetabolomicschemoresistance.neoplasmsLiver Neoplasmshistone macroH2A1Interleukin-2 Receptor alpha SubunitForkhead Transcription Factorshepatocellular carcinomaMiddle Ageddigestive system diseasesGene Expression Regulation NeoplasticHyaluronan ReceptorsDrug Resistance NeoplasmGene Knockdown TechniquesNeoplastic Stem CellsGlycolysisResearch Paper

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.

yearjournalcountryeditionlanguage
2019-03-19Theranostics
10.7150/thno.35045https://pubmed.ncbi.nlm.nih.gov/31903159