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.
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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 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.
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