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PD-1/PD-L1 and immune-related gene expression pattern in pediatric malignant brain tumors: clinical correlation with survival data in Korean population

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Abstract

Background

PD-L1 expression has been evaluated as a predictive biomarker for immunotherapy in numerous tumor types. However, very limited data are available in pediatric brain tumors. The aim of this study was to characterize PD-1 and PD-L1 expressions of four pediatric malignant brain tumors and gene expression profile.

Methods

This study included 89 pediatric patients receiving standard treatment at Seoul National University Children’s Hospital and Seoul National University Bundang Hospital between 1990 and 2014: atypical teratoid/rhabdoid tumor (AT/RT) 20; ependymoma (EPN) 20; high grade glioma (HGG) 21; and medulloblastoma (MBL) 28. We performed immunohistochemistry assays for PD-1 and PD-L1. To characterize the gene expression, a custom immune-response focused gene panel was used.

Results

PD-1 expression was positive in 7 (35%) AT/RT, 7 (35%) EPN, 4 (19%) HGG, and 3 (11%) MBL patients. PD-L1 expression was positive in 8 (40%) AT/RT, 4 (20%) EPN, and 4 (19%) HGG; negative in all MBL patients. There was no statistically significant difference in the overall survival of PD-L1 positive patients. The gene expression analysis demonstrated differences in two clustering functional categories: cell–cell signaling and antigen presentation pathway.

Conclusions

AT/RT, EPN, and HGG showed a relatively higher expression rate of PD-L1 (19–40%). This suggests these tumor types might be good candidates for PD-1 checkpoint blockade. We determined that gene expression may potentially serve as a molecular tool in predicting which patients will respond to immunotherapy. Further investigation is required to better understand the predictive and prognostic role of PD-L1 in pediatric brain tumors.

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Funding

This study was supported by research funding from Merck Sharp & Dohme Corp. (06-2014-249, to Chae-Yong Kim and 06-2015-0060, to Seung-Ki Kim).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam, South Korea

    Kihwan Hwang, Eun Jin Choi, Jung Ho Han & Chae-Yong Kim

  2. Department of Neurosurgery, Dongguk University Ilsan Hospital, Goyang, South Korea

    Eun Jung Koh

  3. Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul, South Korea

    Tae Hee Kang, Kyu-Chang Wang & Seung-Ki Kim

  4. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea

    Gheeyoung Choe

  5. Department of Pathology, Seoul National University Hospital, Seoul, South Korea

    Sung-Hye Park

  6. Merck Sharp & Dohme, Kenilworth, NJ, USA

    Jennifer Holmes Yearley, Lakshmanan Annamalai, Wendy Blumenschein, Manjiri Sathe & Terri McClanahan

  7. Yonsei Song-Dang Institute for Cancer Research, Seoul, South Korea

    Hun Jung

  8. Department of Neurosurgery, Seoul National University College of Medicine, Seoul, South Korea

    Jung Ho Han, Kyu-Chang Wang, Seung-Ki Kim & Chae-Yong Kim

Authors
  1. Kihwan Hwang
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  13. Hun Jung
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Corresponding authors

Correspondence to Seung-Ki Kim or Chae-Yong Kim.

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Conflict of interest

Jennifer H Yearley, Lakshmanan Annamalai, Wendy Blumenschein, Manjiri Sathe, and Terrill McClanahan are employees of Merck Sharp & Dohme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Hwang, K., Koh, E.J., Choi, E.J. et al. PD-1/PD-L1 and immune-related gene expression pattern in pediatric malignant brain tumors: clinical correlation with survival data in Korean population. J Neurooncol 139, 281–291 (2018). https://doi.org/10.1007/s11060-018-2886-5

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