Increased Radiation-Associated T-Cell Infiltration in Recurrent IDH-Mutant Glioma

• Main Authors: Anastasia Makarevic, Carmen Rapp, Steffen Dettling, David Reuss, Christine Jungk, Amir Abdollahi, Andreas von Deimling, Andreas Unterberg, Christel Herold-Mende, Rolf Warta
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: International Journal of Molecular Sciences
• Subjects: lower-grade glioma; T-cell infiltration; TissueFAXS; primary tumors; recurrent tumors; radiotherapy
• Online Access: https://www.mdpi.com/1422-0067/21/20/7801

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 (<i>n</i> = 78) and recurrent (<i>n</i> = 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.