The detection of CMV pp65 and IE1 in glioblastoma multiforme

Kenneth G. Lucas, Lei Bao, Richard Bruggeman, Kimberly Dunham, Charles Specht

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Abstract

Glioblastoma multiforme (GBM) is a highly lethal brain tumor affecting children and adults, with the majority of affected individuals dying from their disease by 2 years following diagnosis. Other groups have reported the association of cytomegalovirus (CMV) with GBM, and we sought to confirm these findings in a large series of patients with primary GBM from our institution. Immunohistochemical analysis of paraffin embedded tissue sections was performed on 49 newly diagnosed GBM tumors, the largest series reported to date. We confirmed the presence of CMV pp65 on 25/49 (51%) and of IE1 on 8/49 (16%) of these tumors. While pp65 and IE1 are generally found in the nucleus of cells that are permissibly infected by CMV, GBM in this series had mostly cytoplasmic staining, with only 16% having nuclear staining for one or both of these antigens. We infected GBM cell lines with a laboratory strain of CMV, and found that most of the staining was cytoplasmic, with some perinuclear localization of IE1. To test the potential for CMV infected GBM cells to be recognized by CMV pp65 and IE1 specific cytotoxic T lymphocytes (CTL), we used CMV infected GBM cell lines in cytotoxicity assays with human leukocyte antigen partially matched CMV CTL. Lysis of CMV infected GBM tumor cells was accentuated by pre-treating these cell lines with either the demethylating agent decitabine or interferon-γ, both of which were shown to increase MHC Class I and II expression on tumor cells in vitro. These studies confirm the presence of CMV pp65 or IE1 on approximately half of GBM, with the possibility that CMV positive tumor cells can be recognized by CMV pp65/IE1 specific T cells.

Original languageEnglish (US)
Pages (from-to)231-238
Number of pages8
JournalJournal of Neuro-Oncology
Volume103
Issue number2
DOIs
StatePublished - Jun 1 2011

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Glioblastoma
Cytomegalovirus
decitabine
Cytotoxic T-Lymphocytes
Neoplasms
Staining and Labeling
Cell Line
HLA Antigens
Cell Nucleus
Brain Neoplasms
Paraffin
Interferons
T-Lymphocytes
Antigens

All Science Journal Classification (ASJC) codes

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Lucas, Kenneth G. ; Bao, Lei ; Bruggeman, Richard ; Dunham, Kimberly ; Specht, Charles. / The detection of CMV pp65 and IE1 in glioblastoma multiforme. In: Journal of Neuro-Oncology. 2011 ; Vol. 103, No. 2. pp. 231-238.
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The detection of CMV pp65 and IE1 in glioblastoma multiforme. / Lucas, Kenneth G.; Bao, Lei; Bruggeman, Richard; Dunham, Kimberly; Specht, Charles.

In: Journal of Neuro-Oncology, Vol. 103, No. 2, 01.06.2011, p. 231-238.

Research output: Contribution to journalArticle

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