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Topic: Neuroimmunology and Cancer

A potential role of karyopherin a2 in the

impaired maturation of dendritic cells observed

in glioblastoma patients

Konstantinos Gousias , Alexander von Ruecker , Gerrit H. Gielen , Pitt Niehusmann , Andreas Waha ,
4
4
1,2
3
4
Hartmut Vatter , Matthias Simon 1
1
1 Department of Neurosurgery, University Hospital of Bonn, Sigmund‑Freud‑Strasse 25, 53105 Bonn, Germany.
2 Department of Neurosurgery, University Hospital of Bochum, Bergmannsheil, Bürkle‑de‑la‑Camp‑Platz 1, 44789 Bochum,
Germany
3 Department of Pathology, University Hospital of Bonn, Sigmund‑Freud‑Strasse 25, 53105 Bonn, Germany.
4 Department of Neuropathology, University Hospital of Bonn, Sigmund‑Freud‑Strasse 25, 53105 Bonn, Germany.
ABSTRA CT

Aim: Patients with glioblastomas demonstrate well‑documented immunological impairments including decreased numbers of
mature dendritic cells (DCs). Recent data identified karyopherin a2 (KPNA2), a nucleocytoplasmic shuttling receptor, as diagnostic
and prognostic biomarker for gliomas. The aim of this ongoing study is to correlate parameters of immunity and nucleocytoplasmic
transport in glioblastoma patients. Methods: We preoperatively collected serum from 17 patients with glioblastomas and determined
DC subsets (HLA DR+ Lin‑, CD34‑, CD45+, CD123+, CD11+ were analyzed) using a 6‑color flow cytometry panel. Expression levels
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of KPNA2 and nuclear accumulation of p53 were evaluated semi‑quantitatively by immunohistochemistry. O ‑methylguanine DNA
methyltransferase (MGMT) and isocitrate dehydrogenase‑1 (IDH‑1) status were assessed by pyrosequencing and immunohistochemistry,
respectively. Results: Median expression levels for both KPNA2 and p53 were 5‑10%. IDH‑1‑R132H mutation and MGMT promoter
hypermethylation was detected in 3/16 and 1/9 patients, respectively. Mean counts of total mature DCs, myeloid DCs and plasmacytoid
DCs were 9.6, 2.1, 3.4 cells/μL. A preliminary analysis suggests an association between low KPNA2 nuclear expression and increased
numbers of mature DCs. However, this correlation did not reach statistical significance so far (P = 0.077). Conclusion: Our preliminary
data may indicate a role of KPNA2 in the impaired maturation of DCs observed in glioblastoma patients.
Key words: Glioblastomas, isocitrate dehydrogenase‑1, karyopherin a2, mature dendritic cells, O ‑methylguanine DNA
6
methyltransferase, p53

INTRODUCTION antigens/tumor cells they undergo maturation, i.e.,
they upregulate major histocompatibility complex
Patients with glioblastomas demonstrate class II and co-stimulatory molecules at cell surface,
well-documented impairments of their immune system, they migrate to T cell rich zones and secrete cytokines
including reduced values of mature dendritic cells to induce an antigen-specific T cell response. [7]
(DCs). [1-4] DCs is the most potent antigen-presenting
cell population and therefore key regulators of adaptive DCs maturation may be mediated by known signaling
immunity. Apart from their defense against infectious pathways/transcription factors, for instance,
diseases they may also mediate antitumor responses. [5,6] nuclear factor-κB (NF-κB), which is triggered after
Their maturation/differentiation plays a pivotal role activation of the toll-like receptors (TLRs) by invading
in their function. After recognizing and capturing microorganisms. Once in the nucleus, NF-κB may
[7]
induce the transcription of various genes involving in
Access this article online immune and inflammatory responses. Nuclear import
[8]
Quick Response Code: of NF-κB is mediated by the karyopherin a2/importin
Website: unit 2 complex (KPNA2), a well-studied member of the
www.nnjournal.net
family of karyopherins. [9]
DOI:
10.4103/2347-8659.149396 Karyopherins are nucleocytoplasmatic shuttling
receptors and comprise importins and exportins. They

Corresponding Author: Dr. Konstantinos Gousias, Department of Neurosurgery, University Hospital of Bonn,
Sigmund‑Freud‑Strasse 25, 53105 Bonn, Germany. E‑mail: kostasgousias@yahoo.com

8 Neuroimmunol Neuroinflammation | Volume 2 | Issue 1 | January 15, 2015