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Cancer Immunology, Immunotherapy

, Volume 68, Issue 2, pp 305–318 | Cite as

Tumor-infiltrating immune cell subpopulations and programmed death ligand 1 (PD-L1) expression associated with clinicopathological and prognostic parameters in ependymoma

  • Soo Jeong NamEmail author
  • Young-Hoon Kim
  • Ji Eun Park
  • Young-shin Ra
  • Shin Kwang Khang
  • Young Hyun Cho
  • Jeong Hoon Kim
  • Chang Ohk SungEmail author
Original Article
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Abstract

Ependymomas are biologically and clinically heterogeneous tumors of the central nervous system that have variable clinical outcomes. The status of the tumor immune microenvironment in ependymoma remains unclear. Immune cell subsets and programmed death ligand 1 (PD-L1) expression were measured in 178 classical ependymoma cases by immunohistochemistry using monoclonal antibodies that recognized tumor-infiltrating lymphocyte subsets (TILs; CD3, CD4, CD8, FOXP3, and CD20), tumor-associated macrophages (TAMs; CD68, CD163, AIF1), indoleamine 2,3-dioxygenase (IDO)+ cells and PD-L1-expressing tumor cells. Increases in CD3+ and CD8+ cell numbers were associated with a prolonged PFS. In contrast, increased numbers of FOXP3+ and CD68+ cells and a ratio of CD163/AIF1+ cells were significantly associated with a shorter PFS. An increase in the IDO+ cell number was associated with a significantly longer PFS. To consider the quantities of TILs, TAMs, and IDO+ cells together, the cases were clustered into 2 immune cell subgroups using a k-means clustering analysis. Immune cell subgroup A, which was defined by high CD3+, low CD68+ and high IDO+ cell counts, predicted a favorable PFS compared to subgroup B by univariate and multivariate analyses. We found six ependymoma cases expressing PD-L1. All these cases were supratentorial ependymoma, RELA fusion-positive (ST-RELA). PD-L1 expression showed no prognostic significance. This study showed that the analysis of tumor-infiltrating immune cells could aid in predicting the prognosis of ependymoma patients and in determining therapeutic strategies to target the tumor microenvironment. PD-L1 expression in the ST-RELA subgroup suggests that this marker has a potential added value for future immunotherapy treatments.

Keywords

Immune microenvironment Tumor-infiltrating lymphocytes Tumor-associated macrophages Indoleamine 2,3-dioxygenase Ependymoma Programmed death ligand 1 

Abbreviations

AIF1

Allograft inflammatory factor 1

CNS

Central nervous system

GTS

Gross total resection

ICC

Intraclass correlation coefficient

KPS

Karnofsky Performance Scale

NF2

Neurofibromatosis type 2

PF

Posterior fossa

PF-A

Posterior fossa ependymoma, group A

PF-B

Posterior fossa ependymoma, group B

SP

Spinal cord

ST

Supratentorial

ST-RELA

Supratentorial ependymoma, RELA fusion-positive

STR

Subtotal resection

TAMs

Tumor-associated macrophages/microglia

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Notes

Author contributions

Study conception and design were performed by SJN and COS. SJN, COS, and SKK reviewed the pathological materials according to current WHO criteria. SJN, Y-HK, and JEP reviewed and obtained detailed clinical data. Y-sR organized cohort of pediatric ependymoma patients and obtained clinical data from the medical records. YHC, and JHK organized cohort of adult ependymoma patients and obtained clinical data from the medical records. Statistical analysis was performed by SJN and COS. SJN prepared the initial manuscript. All co-authors made substantial contributions to the rewriting of the manuscript, review, and approval.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval and ethical standards.

This study was performed with archived paraffin-embedded tissue samples. This study was approved by the Asan Medical Center Institutional review board (approval number 2016 − 1197) and was conducted in accordance with the Declaration of Helsinki.\

Informed consent

Informed consent by individual patients could not be given, as the study only included paraffin-embedded archived tissue. With the approval of the ethical committee, informed consent was not required because all patient data were anonymized.

Supplementary material

262_2018_2278_MOESM1_ESM.pdf (1.2 mb)
Supplementary material 1 (PDF 1220 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyAsan Medical CenterSeoulSouth Korea
  2. 2.Department of NeurosurgeryAsan Medical CenterSeoulSouth Korea
  3. 3.Department of RadiologyAsan Medical CenterSeoulSouth Korea

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