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Journal of Neuro-Oncology

, Volume 133, Issue 2, pp 277–285 | Cite as

Assessment of PD-1 positive cells on initial and secondary resected tumor specimens of newly diagnosed glioblastoma and its implications on patient outcome

  • Tsubasa Miyazaki
  • Eiichi Ishikawa
  • Masahide Matsuda
  • Hiroyoshi Akutsu
  • Satoru Osuka
  • Noriaki Sakamoto
  • Shingo Takano
  • Tetsuya Yamamoto
  • Koji Tsuboi
  • Akira Matsumura
Laboratory Investigation

Abstract

Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma. We investigated 16 patients, ranging in age from 14 to 65 years, with histologically verified WHO grade IV GBM, whose original tumor was resected between 2008 and 2014, and treated with fractionated radiotherapy and temozolomide. Four patients who were treated with immunotherapy using autologous formalin-fixed tumor vaccine were enrolled. All of the patients underwent secondary resection after tumor recurrence within 24 months. We carried out an immunohistochemical examination of the initial and secondary resected tumors from patients using a panel of immune system molecular markers, and assessed whether marker expression correlated with clinical outcomes. CD3, CD8 and PD-1 on tumor-infiltrating lymphocytes was significantly increased in secondary resected specimens compared with initially resected specimens (p ≤ 0.05). All patients expressed PD-L1 on tumor cells in initial and secondary resection specimens. Patients were divided into high or low expression group by median IHC score of PD-1 on initial or secondary resected specimens. No significant differences in patient outcomes were observed between high and low PD-1 or PD-L1 groups of initially resected specimens. In high expression group of secondary resected specimens, most patients score had increased which compared with initial resected tumor specimens. The PD-1 high expression score group of secondary resected specimens was associated with long progression-free survival and short survival after recurrence. PD-L1 expression was detected in almost all initial and secondary specimens. Patients with high PD-1 expression of secondary specimen had bad prognosis after secondary resection. PD-1/PD-L1 pathway may be associated with patient outcome after second surgery of glioblastoma.

Keywords

Glioma immunotherapy PD-1 Recurrence 

Abbreviations

FRT

Fractionated radiotherapy

GBM

Glioblastoma multiforme

GRZB

Granzyme B

IDH1

Isocitrate dehydrogenase-1

IHC

Immunohistochemistry

MGMT

O6-methylguanine-DNA methyltransferase

MHC

Major histocompatibility complex

PD-1

Programmed cell death 1

PD-L1

PD-1 ligand

AFTV

Autologous formalin-fixed tumor vaccine

OS

Overall survival

PFS

Progression-free survival

TIL

Tumor-infiltrating lymphocytes

TMZ

Temozolomide

Notes

Acknowledgements

This study was supported by projects for Grant-in-Aid for Scientific Research of Japan and promoting practical applications of advanced medical technologies in Tsukuba University Hospital. Some of the materials for the tumor vaccine was provided by Cell-Medicine, Inc. (CMI) free of charge. CMI is a venture company for research and development of immunotherapy born from RIKEN (The Institute of Physical and Chemical Research) and University of Tsukuba in Japan. T.M and K.T. are members/employees of CMI; and K.T is a stockholder.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Tsubasa Miyazaki
    • 1
    • 2
  • Eiichi Ishikawa
    • 1
  • Masahide Matsuda
    • 1
  • Hiroyoshi Akutsu
    • 1
  • Satoru Osuka
    • 3
  • Noriaki Sakamoto
    • 4
  • Shingo Takano
    • 1
  • Tetsuya Yamamoto
    • 1
  • Koji Tsuboi
    • 2
    • 5
  • Akira Matsumura
    • 1
  1. 1.Department of Neurosurgery, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  2. 2.Cell-Medicine, Inc.TsukubaJapan
  3. 3.Department of Neurosurgery, Winship Cancer InstituteEmory University School of MedicineAtlantaUSA
  4. 4.Department of Pathology, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  5. 5.Proton Medical Research Center, Faculty of MedicineUniversity of TsukubaTsukubaJapan

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