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Implications of immune cells in oncolytic herpes simplex virotherapy for glioma

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Abstract

Despite current progress in treatment, glioblastoma (GBM) remains a lethal primary malignant tumor of the central nervous system. Although immunotherapy has recently achieved remarkable survival effectiveness in multiple malignancies, none of the immune checkpoint inhibitors (ICIs) for GBM have shown anti-tumor efficacy in clinical trials. GBM has a characteristic immunosuppressive tumor microenvironment (TME) that results in the failure of ICIs. Oncolytic herpes simplex virotherapy (oHSV) is the most advanced United States Food and Drug Administration-approved virotherapy for advanced metastatic melanoma patients. Recently, another oHSV, Delytact®, was granted conditional approval in Japan against GBM, highlighting it as a promising treatment. Since oncolytic virotherapy can recruit abundant immune cells and modify the immune TME, oncolytic virotherapy for immunologically cold GBM will be an attractive therapeutic option for GBM. However, as these immune cells have roles in both anti-tumor and anti-viral immunity, fine-tuning of the TME using oncolytic virotherapy will be important to maximize the therapeutic efficacy. In this review, we discuss the current knowledge of oHSV, with a focus on the role of immune cells as friend or foe in oncolytic virotherapy.

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Acknowledgements

This study was supported by grants-in-aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (No. 21K20803, YO) and research grants from Teraoka Scholarship Foundation to YO.

Funding

This study was supported by grants-in-aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (No. 21K20803, YO) and research grants from Teraoka Scholarship Foundation to YO.

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Authors and Affiliations

  1. Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Yoshihiro Otani & Isao Date

  2. Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX, 77030, USA

    Ji Young Yoo & Balveen Kaur

  3. Department of Neurosurgery, Matsuyama Shimin Hospital, 2-6-5 Otemachi, Matsuyama, Ehime, 790-0067, Japan

    Toshihiko Shimizu

  4. Department of Neurosurgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan

    Kazuhiko Kurozumi

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  1. Yoshihiro Otani
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  2. Ji Young Yoo
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  3. Toshihiko Shimizu
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Correspondence to Yoshihiro Otani.

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Otani, Y., Yoo, J.Y., Shimizu, T. et al. Implications of immune cells in oncolytic herpes simplex virotherapy for glioma. Brain Tumor Pathol 39, 57–64 (2022). https://doi.org/10.1007/s10014-022-00431-8

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