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

Article Article scientifique Article Decitabine Treatment of Glioma-Initiating Cells Enhances Immune Recognition and Killing eng 2016 author Riccadonna Cristina 703976 author Yacoub Maroun Céline 656899 author Vuillefroy De Silly Romain 782322 author Boehler Margaux author Calvo Tardon Marta 778010 author Jueliger Simone author Taverna Pietro author Barba Leticia 632178 author Marinari Eliana 841772 author Pellegatta Serena author Bassoy Esen 757703 author Martinvalet Denis 713869 author Dietrich Pierre-Yves 96532 author Walker Paul Richard 0000-0001-8999-6366 104900 e0162105 10.1371/journal.pone.0162105 1932-6203 http://dx.plos.org/10.1371/journal.pone.0162105 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. Dewey 616 56 Département de médecine 221 false 401 Immunobiologie des tumeurs du cerveau 669 27 Immunothérapie des cancers 42 557 ROS in CTL mediated cell death : from mechanism to applications 898 PloS one 11 8 5ab82c38-326f-463e-ab15-0e82da470b2e Article (Published version) Public Riccadonna.pone.0162105.PDF 2062367 application/pdf CC BY openAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Decitabine Treatment of Glioma-Initiating Cells Enhances Immune Recognition and Killing	PloS one			2016	673	710

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