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

Risultato della ricerca: Article

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.
Lingua originaleEnglish
pagine (da-a)910-924
Numero di pagine15
RivistaTheranostics
Volume10
Stato di pubblicazionePublished - 2020

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Regulatory T-Lymphocytes
Histones
Hepatocellular Carcinoma
Neoplastic Stem Cells
Immune Evasion
Tumor Microenvironment
Conditioned Culture Medium
Immune System
T-Lymphocytes

All Science Journal Classification (ASJC) codes

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

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Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation. / Rappa, Francesca; Tsochatzis, Emmanuel; Luong, Tu Vinh; Lo Re, Oriana; Van Haele, Matthias; Giallongo, Sebastiano; Li Volti, Giovanni; Drovakova, Adela; Sanna, Paola; Vinciguerra, Manlio; Li Volti, Giovanni; Roskams, Tania; Mazza, Tommaso.

In: Theranostics, Vol. 10, 2020, pag. 910-924.

Risultato della ricerca: Article

Rappa, F, Tsochatzis, E, Luong, TV, Lo Re, O, Van Haele, M, Giallongo, S, Li Volti, G, Drovakova, A, Sanna, P, Vinciguerra, M, Li Volti, G, Roskams, T & Mazza, T 2020, 'Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation', Theranostics, vol. 10, pagg. 910-924.
Rappa, Francesca ; Tsochatzis, Emmanuel ; Luong, Tu Vinh ; Lo Re, Oriana ; Van Haele, Matthias ; Giallongo, Sebastiano ; Li Volti, Giovanni ; Drovakova, Adela ; Sanna, Paola ; Vinciguerra, Manlio ; Li Volti, Giovanni ; Roskams, Tania ; Mazza, Tommaso. / Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation. In: Theranostics. 2020 ; Vol. 10. pagg. 910-924.
@article{22e1a54928ea471cb310db605521bc78,
title = "Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation",
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.",
keywords = "adaptive immune system, chemoresistance., hepatocellular carcinoma, histone macroH2A1",
author = "Francesca Rappa and Emmanuel Tsochatzis and Luong, {Tu Vinh} and {Lo Re}, Oriana and {Van Haele}, Matthias and Sebastiano Giallongo and {Li Volti}, Giovanni and Adela Drovakova and Paola Sanna and Manlio Vinciguerra and {Li Volti}, Giovanni and Tania Roskams and Tommaso Mazza",
year = "2020",
language = "English",
volume = "10",
pages = "910--924",
journal = "Theranostics",
issn = "1838-7640",
publisher = "Ivyspring International Publisher",

}

TY - JOUR

T1 - Loss of histone macroH2A1 in hepatocellular carcinoma cells promotes paracrine-mediated chemoresistance and CD4+CD25+FoxP3+ regulatory T cells activation

AU - Rappa, Francesca

AU - Tsochatzis, Emmanuel

AU - Luong, Tu Vinh

AU - Lo Re, Oriana

AU - Van Haele, Matthias

AU - Giallongo, Sebastiano

AU - Li Volti, Giovanni

AU - Drovakova, Adela

AU - Sanna, Paola

AU - Vinciguerra, Manlio

AU - Li Volti, Giovanni

AU - Roskams, Tania

AU - Mazza, Tommaso

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - adaptive immune system

KW - chemoresistance.

KW - hepatocellular carcinoma

KW - histone macroH2A1

UR - http://hdl.handle.net/10447/392894

M3 - Article

VL - 10

SP - 910

EP - 924

JO - Theranostics

JF - Theranostics

SN - 1838-7640

ER -