Tumor-infiltrating immune cell subpopulations and programmed death ligand 1 (PD-L1) expression associated with clinicopathological and prognostic parameters in ependymoma
| Autor: | Soo Jeong Nam, Young Hoon Kim, Chang Ohk Sung, Young-Shin Ra, Shin Kwang Khang, Young Hyun Cho, Jeong Hoon Kim, Ji Eun Park |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Ependymoma Cancer Research Adolescent medicine.medical_treatment Immunology Kaplan-Meier Estimate B7-H1 Antigen Young Adult 03 medical and health sciences Lymphocytes Tumor-Infiltrating 0302 clinical medicine Immune system T-Lymphocyte Subsets Biomarkers Tumor Tumor Microenvironment Humans Immunology and Allergy Medicine Child Aged CD20 Tumor microenvironment biology business.industry Tumor-infiltrating lymphocytes Infant Newborn Infant FOXP3 Immunotherapy Middle Aged Prognosis medicine.disease Oncology Child Preschool biology.protein Cancer research Female business CD8 030215 immunology |
| Zdroj: | Cancer Immunology, Immunotherapy. 68:305-318 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-018-2278-x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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