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Journal of Neuro-Oncology

, Volume 137, Issue 2, pp 249–257 | Cite as

Analysis of immunobiologic markers in primary and recurrent glioblastoma

  • Maryam RahmanEmail author
  • Jesse Kresak
  • Changlin Yang
  • Jianping Huang
  • Wesley Hiser
  • Paul Kubilis
  • Duane Mitchell
Laboratory Investigation

Abstract

Glioblastoma (GBM) generates a varied immune response and understanding the immune microenvironment may lead to novel immunotherapy treatments modalities. The goal of this study was to evaluate the expression of immunologic markers of potential clinical significance in primary versus recurrent GBM and assess the relationship between these markers and molecular characteristics of GBM. Human GBM samples were evaluated and analyzed with immunohistochemistry for multiple immunobiologic markers (CD3, CD8, FoxP3, CD68, CD163, PD1, PDL1, CTLA4, CD70). Immunoreactivity was analyzed using Aperio software. Degree of strong positive immunoreactivity within the tumor was compared to patient and tumor characteristics including age, gender, MGMT promoter methylation status, and ATRX, p53, and IDH1 mutation status. Additionally, the TCGA database was used to perform similar analysis of these factors in GBM using RNA-seq by expectation–maximization. Using odds ratios, IDH1 mutated GBM had statistically significant decreased expression of CD163 and CD70 and a trend for decreased PD1, CTLA4, and Foxp3. ATRX-mutated GBMs exhibited statistically significant increased CD3 immunoreactivity, while those with p53 mutations were found to have significantly increased CTLA4 immunoreactivity. The odds of having strong CD8 and CD68 reactivity was significantly less in MGMT methylated tumors. No significant difference was identified in any immune marker between the primary and recurrent GBM, nor was a significant change in immunoreactivity identified among age intervals. TCGA analysis corroborated findings related to the differential immune profile of IDH1 mutant, p53 mutant, and MGMT unmethylated tumors. Immunobiologic markers have greater association with the molecular characteristics of the tumor than with primary/recurrent status or age.

Keywords

Immune infiltrates Tumor infiltrating lymphocytes Immunobiologic markers High grade glioma Glioblastoma 

Notes

Acknowledgements

This work was funded by the Florida Center for Brain Tumor Research. We would like to acknowledge Barbara Frentzen for her work in obtaining samples for analysis through the FCBTR.

Supplementary material

11060_2017_2732_MOESM1_ESM.tif (190 kb)
Supplementary Figure 1. Effect of Recurrent versus Primary tumor status on immune marker expression. Circled odds ratio point estimates differ significantly from one at α=0.05 (TIF 190 KB)
11060_2017_2732_MOESM2_ESM.tif (192 kb)
Supplementary Figure 2. Change in Immune Marker Expression per 10-Year Age Increase. Circled odds ratio point estimates differ significantly from one at α=0.05 (TIF 192 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyUniversity of FloridaGainesvilleUSA
  2. 2.Department of NeurosurgeryUniversity of FloridaGainesvilleUSA
  3. 3.University of Florida Brain Tumor Immunotherapy ProgramUniversity of FloridaGainesvilleUSA

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