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Decitabine Treatment of Glioma-Initiating Cells Enhances Immune Recognition and Killing

Contributors

Riccadonna, Cristina; Yacoub Maroun, Céline; Vuillefroy De Silly, Romain; Boehler, Margaux; Calvo Tardon, Marta; Jueliger, Simone; Taverna, Pietro; Barba, Leticia; Marinari, Eliana; Pellegatta, Serena; Bassoy, Esen; Martinvalet, Denis; Dietrich, Pierre-Yves; Walker, Paul Richard

Published in

PloS one, vol. 11, no. 8, e0162105

Publication date

2016

Abstract

Malignant gliomas are aggressive brain tumours with very poor prognosis. The majority of glioma cells are differentiated (glioma-differentiated cells: GDCs), whereas the smaller population (glioma-initiating cells, GICs) is undifferentiated and resistant to conventional therapies. Therefore, to better target this pool of heterogeneous cells, a combination of diverse therapeutic approaches is envisaged. Here we investigated whether the immunosensitising properties of the hypomethylating agent decitabine can be extended to GICs. Using the murine GL261 cell line, we demonstrate that decitabine augments the expression of the death receptor FAS both on GDCs and GICs. Interestingly, it had a higher impact on GICs and correlated with an enhanced sensitivity to FASL-mediated cell death. Moreover, the expression of other critical molecules involved in cognate recognition by cytotoxic T lymphocytes, MHCI and ICAM-1, was upregulated by decitabine treatment. Consequently, T-cell mediated killing of both GDCs and GICs was enhanced, as was T cell proliferation after reactivation. Overall, although GICs are described to resist classical therapies, our study shows that hypomethylating agents have the potential to enhance glioma cell recognition and subsequent destruction by immune cells, regardless of their differentiation status. These results support the development of combinatorial treatment modalities including epigenetic modulation together with immunotherapy in order to treat heterogenous malignancies such as glioblastoma.

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

RICCADONNA, Cristina et al. Decitabine Treatment of Glioma-Initiating Cells Enhances Immune Recognition and Killing. In: PloS one, 2016, vol. 11, n° 8, p. e0162105. doi: 10.1371/journal.pone.0162105

Main files (1)

Article (Published version)
CC BY

Identifiers

Additional URL for this publication

http://dx.plos.org/10.1371/journal.pone.0162105

Journal ISSN

1932-6203
684views
739downloads

Technical informations

Creation

23/11/2016 14:57:00

First validation

23/11/2016 14:57:00

Update

15/03/2023 01:00:41

Status update

15/03/2023 01:00:41

Last indexation

31/10/2024 05:15:03
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