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Immune landscapes associated with different glioblastoma molecular subtypes.

TitleImmune landscapes associated with different glioblastoma molecular subtypes.
Publication TypeJournal Article
Year of Publication2019
AuthorsMartinez-Lage M, Lynch TM, Bi Y, Cocito C, Way GP, Pal S, Haller J, Yan RE, Ziober A, Nguyen A, Kandpal M, O'Rourke DM, Greenfield JP, Greene CS, Davuluri RV, Dahmane N
JournalActa Neuropathol Commun
Volume7
Issue1
Pagination203
Date Published2019 11 29
ISSN2051-5960
KeywordsAntigens, CD20, Brain Neoplasms, Glioblastoma, Humans, Immunity, Cellular, Tumor Microenvironment
Abstract

Recent work has highlighted the tumor microenvironment as a central player in cancer. In particular, interactions between tumor and immune cells may help drive the development of brain tumors such as glioblastoma multiforme (GBM). Despite significant research into the molecular classification of glioblastoma, few studies have characterized in a comprehensive manner the immune infiltrate in situ and within different GBM subtypes.In this study, we use an unbiased, automated immunohistochemistry-based approach to determine the immune phenotype of the four GBM subtypes (classical, mesenchymal, neural and proneural) in a cohort of 98 patients. Tissue Micro Arrays (TMA) were stained for CD20 (B lymphocytes), CD5, CD3, CD4, CD8 (T lymphocytes), CD68 (microglia), and CD163 (bone marrow derived macrophages) antibodies. Using automated image analysis, the percentage of each immune population was calculated with respect to the total tumor cells. Mesenchymal GBMs displayed the highest percentage of microglia, macrophage, and lymphocyte infiltration. CD68 and CD163 cells were the most abundant cell populations in all four GBM subtypes, and a higher percentage of CD163 cells was associated with a worse prognosis. We also compared our results to the relative composition of immune cell type infiltration (using RNA-seq data) across TCGA GBM tumors and validated our results obtained with immunohistochemistry with an external cohort and a different method. The results of this study offer a comprehensive analysis of the distribution and the infiltration of the immune components across the four commonly described GBM subgroups, setting the basis for a more detailed patient classification and new insights that may be used to better apply or design immunotherapies for GBM.

DOI10.1186/s40478-019-0803-6
Alternate JournalActa Neuropathol Commun
PubMed ID31815646
PubMed Central IDPMC6902522
Grant ListHG000046. / NH / NIH HHS / United States
T32 AG000255 / AG / NIA NIH HHS / United States
GBMF4552 / / Gordon and Betty Moore Foundation / International
R01 LM011297 / LM / NLM NIH HHS / United States
UL1 TR001422 / TR / NCATS NIH HHS / United States
NS095411 / NH / NIH HHS / United States
R01 NS093120 / NS / NINDS NIH HHS / United States