Abstract
Subependymomas are usually treated with surgical resection; however, no standard, defined alternative medical therapy is recommended for patients who are not surgical candidates, owing to a paucity of molecular, immunological, and genetic characterization. To address this, an ex vivo functional analysis of the immune microenvironment in subependymoma was conducted, a subependymoma cytokine/chemokine microarray was constructed for the evaluation of operational immune and molecular pathways, and a subependymoma cell line was derived and used to test a variety of cytotoxic agents that target operational pathways identified in subependymoma. We found that immune effectors are detectable within the microenvironment of subependymoma; however, marked immune suppression is not observed. The subependymoma tissue microarrays demonstrated tumor expression of p53, MDM2, HIF-1α, topoisomerase II-β, p-STAT3, and nucleolin, but not EGFRvIII, EphA2, IL-13RA2, CMV, CTLA-4, FoxP3, PD-1, PD-L1, EGFR, PDGF-α, PDGF-β, PDGFR-α, PDGFR-β, PTEN, IGFBP2, PI3K, MDM4, IDH1, mTOR, or Jak2. A topoisomerase inhibitor (WP744, IC50=0.83μM) and a p-STAT3/HIF-1α inhibitor (WP1066, IC50=3.15μM) demonstrated a growth inhibition of the subependymoma cell proliferation. Cumulatively, these data suggest that those agents that interfere with oncogenes operational in subependymoma may have clinical impact.
Original language | English (US) |
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Pages (from-to) | 168-175 |
Number of pages | 8 |
Journal | Journal of Neuroimmunology |
Volume | 277 |
Issue number | 1-2 |
DOIs | |
State | Published - Dec 15 2014 |
Keywords
- Ependymoma
- Immunotherapy
- Noninvasive
- Subependymoma
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Neurology
- Clinical Neurology
MD Anderson CCSG core facilities
- Tissue Biospecimen and Pathology Resource
- Clinical Trials Office