oHSV-P10 reduces glioma stem cell enrichment after oncolytic HSV therapy

Upasana Sahu; Matthew P Mullarkey; Guangsheng Pei; Zhongming Zhao; Bangxing Hong; Balveen Kaur

doi:10.1016/j.omto.2023.03.003

oHSV-P10 reduces glioma stem cell enrichment after oncolytic HSV therapy

Mol Ther Oncolytics. 2023 Apr 3:29:30-41. doi: 10.1016/j.omto.2023.03.003. eCollection 2023 Jun 15.

Authors

Upasana Sahu¹, Matthew P Mullarkey¹, Guangsheng Pei², Zhongming Zhao², Bangxing Hong¹, Balveen Kaur¹

Affiliations

¹ Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
² Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Abstract

Longstanding evidence implicate glioma stem-like cells as the main drivers contributing toward glioblastoma (GBM) therapy resistance and tumor recurrence. Although oncolytic herpes simplex virus (oHSV) viral therapy is a promising biological therapy recently approved for melanoma (in the United States and Europe) and GBM (in Japan); however, the impact of this therapy on GBM stem-like cells (GSCs) is understudied. Here we show that post-oHSV virotherapy activated AKT signaling results in an enrichment of GSC signatures in glioma, which mimics the enrichment in GSC observed after radiation treatment. We also uncovered that a second-generation oncolytic virus armed with PTEN-L (oHSV-P10) decreases this by moderating IL6/JAK/STAT3 signaling. This ability was retained in the presence of radiation treatment and oHSV-P10-sensitized intracranial GBM to radiotherapy. Collectively, our findings uncover potential mechanisms to overcome GSC-mediated radiation resistance via oHSV-P10.

Keywords: IL6; MT: Regular Issue; STAT3; glioblastoma; glioma stem cells; irradiation; oncolytic HSV1.

Abstract

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