Increased radiation-associated T-cell infiltration in recurrent IDH-mutant glioma

Most gliomas are associated with a fatal prognosis and remain incurable because of their infiltrative growth. Consequently, the addition of immunotherapy to conventional therapy may improve patient outcomes. Here, we analyzed T-cell infiltration and, therefore, a major prerequisite for successful im...

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Main Authors: Makarevic, Anastasia (Author) , Rapp, Carmen (Author) , Dettling, Steffen (Author) , Reuss, David (Author) , Jungk, Christine (Author) , Abdollahi, Amir (Author) , Deimling, Andreas von (Author) , Unterberg, Andreas (Author) , Herold-Mende, Christel (Author) , Warta, Rolf (Author)
Format: Article (Journal)
Language:English
Published: 21 October 2020
In: International journal of molecular sciences
Year: 2020, Volume: 21, Issue: 20
ISSN:1422-0067
DOI:10.3390/ijms21207801
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/ijms21207801
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1422-0067/21/20/7801
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Author Notes:Anastasia Makarevic, Carmen Rapp, Steffen Dettling, David Reuss, Christine Jungk, Amir Abdollahi, Andreas von Deimling, Andreas Unterberg, Christel Herold-Mende and Rolf Warta

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520 |a Most gliomas are associated with a fatal prognosis and remain incurable because of their infiltrative growth. Consequently, the addition of immunotherapy to conventional therapy may improve patient outcomes. Here, we analyzed T-cell infiltration and, therefore, a major prerequisite for successful immunotherapy in a series of primary (n = 78) and recurrent (n = 66) isocitrate dehydrogenase (IDH)-mutant glioma and their changes following treatment with radio- and/or chemotherapy. After multicolor immunofluorescence staining, T cells were counted in entire tumor sections using a software-based setup. Newly diagnosed diffuse IDH-mutant gliomas displayed a median T-cell infiltration of 0.99 T cells/mm2 (range: 0–48.97 CD3+ T cells/mm2), which was about two-fold increased for CD3+, helper, and cytotoxic T cells in recurrent glioma. Furthermore, T-cell infiltration of recurrent tumors was associated with the type of adjuvant treatment of the primary tumor. Interestingly, only glioma patients solely receiving radiotherapy presented consistently with increased T-cell infiltration in their recurrent tumors. This was confirmed in a subset of 27 matched pairs. In conclusion, differences in the T-cell infiltration of primary and recurrent gliomas were demonstrated, and evidence was provided for a beneficial long-term effect on T-cell infiltration upon treatment with radiotherapy. 
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