Theranostics 2020; 10(2):910-924. doi:10.7150/thno.35045 This issue
1. International Clinical Research Center, St' Anne's University Hospital, Brno, Czech Republic;
2. Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic;
3. IRCCS Casa Sollievo della Sofferenza, Laboratory of Bioinformatics, San Giovanni Rotondo (FG), Italy;
4. Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy;
5. Department of Histopathology, Royal Free London NHS Foundation Trust, London, United Kingdom;
6. Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy;
7. Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic;
8. Department of Animal Physiology and Immunology, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic;
9. Translational Cell & Tissue Research Unit, Department of Imaging & Pathology, Katholieke Universiteit Leuven, Leuven, Belgium;
10. UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, United Kingdom.
*these authors contributed equally
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.
Keywords: hepatocellular carcinoma, histone macroH2A1, adaptive immune system, chemoresistance.