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No significant imbalances between subgroups of these transcription factors, such as karyopherins,
of KPNA2 and p53 expression as well as MGMT may also affect the maturation procedures.
promoter methylation and IDH-1 mutation status (see
statistical analysis) with respect to age, gender, type Recognition receptors of immature DCs, such as TLRs,
of resection (resection vs. biopsy), preoperative may be triggered by invading microorganisms or
and postoperative KPI, tumor volume, presence of endogenous inflammatory signals and on their turn they
epilepsy (yes/no), neurological deficits (yes/no) may activate signaling pathways/transcription factors,
and eloquence of the tumor location (yes/no) were such as NF-κB, in order to foster their maturation.
seen [Table 3]. This pathway is among others characterized by
the proteolytic processing of NF-κB p100 protein
DISCUSSION to p52 and the translocation of the latter in the
nucleus. [31,32] Lind et al. [31] studied NF-κB pathway
Patients with glioblastomas exhibit well-documented in vivo in alymphoplasia (Aly) and wild type (WT) mice.
immunological abnormalities; in particular, they Aly mouse expresses mutant molecules that prohibit
demonstrate an impaired cellular immunity; that the induction of NF-κB pathway and demonstrate an
is, reduced counts of effector T helper and relative impaired cross-presentation of antigens. Aly failed to
accumulation of suppressive T regulatory cells. [2,4] translocate p52 to the nucleus after activation with
The APC function of DCs, as reflected by the ability CD40, whereas a normal nuclear p52 translocation
to stimulate allogeneic T cells, is also altered/ occurs in WT. [31] The nuclear import of p52 is mediated
diminished. Patients with glioblastomas demonstrate by members of karyopherin family proteins (a1-a5,
[30]
also reduced values of mature DCs compared to patients a7). [9,32]
with gliomas WHO grade I-III or healthy donors. [4]
Karyopherins are nuclear proteins involved in
The maturation of DCs is the key regulator of their APC nucleocytoplasmatic shuttling and have been linked
function, comprises several stages (stem cells/precursors/ to tumorigenesis. KPNA2 has been identified as a
poorly differentiated/highly differentiated not activated/ regulator of DNA repair proteins and an activator of
highly differentiated and activated/apoptosis) and apoptosis pathways. [10-13] Recent data suggested a role
includes the up regulation in the nucleus of MCH for KPNA2, also in gliomagenesis. We have recognized
class II and specific co-stimulatory molecules, such as in two recent works about KPNA2 as an independent
CD11c, CD45, CD83, CD86 and CD123. [7,24-27] This up prognostic factor for OS and PFS in 94 patients with
regulation may be generally triggered by transcription infiltrative astrocytomas WHO grade II-IV as well as
factors/stimuli (macromolecules > 40 kDa), which are in 72 patients with anaplastic gliomas (astrocytomas,
being actively translocated from the cell surface (that is, oligoastrocytomas and oligodendrogliomas WHO
side of “danger signal” production upon recognition of grade III). [14,15] KPNA2 has been also identified as a
invading microorganisms/antigens) into the nucleus. [7,8] prognostic factor in patients with meningiomas [16] as
Consequently, molecules involved in the nuclear import well as in patients with other solid tumors. [17-20]

Table 2: Relative proportions and counts of T‑lymphocytes, T‑helper lymphocytes and DC subsets in our series
Immunological parameter Relative proportion mean (95% CI) Counts (cells/μL) mean (95% CI), median
T cell lymphocytes CD3+ %WBC* 6.58 (3.24‑9.92) 554 (348‑760), 488
T helper lymphocytes CD4+ %WBC 4.16 (1.90‑6.42) 348 (199‑497), 225
DCs HLA DR+/CD34‑/CD45+ %WBC 0.11 (0.05‑0.16) 9.6 (4.3‑14.9), 5.9
pDCs CD123+ CD11c‑ %DC** 28.3 (16.5‑40.1) 3.4 (1.1‑5.8), 1.6
mDCs CD123‑, CD11c+ %DC 15.5 (6.0‑25.1) 2.1 (0.6‑3.6), 0.6
CD123‑, CD11c‑ %DC 54.5 (38.7‑70.3) 10.1 (0.4‑21.4), 2.1
*% WBC: relative proportion of WBCs; **% DC: relative proportion of DCs. DCs: dendritic cells; WBC: white blood cell; CI: confidence interval; HLA: human leukocyte
antigen; DR: diabetic retinopathy

Table 3: Correlations between levels of immunoreactivity (p53 and KPNA2) and clinical characteristics
Variable p53 < 5% vs. ≥ 5%, P KPNA2 < 5% vs. ≥ 5%, P
Males 57.1% vs. 60.0%, n.s* 66.7% vs. 53.8%, n.s
Max tumor diameter ≤ 3 cm 71.4% vs. 25.0%, n.s 33.3% vs. 54.5%, n.s
Resection
Cytoreductive surgery 57.1% vs. 88.9%, n.s 66.7% vs. 83.3%, n.s
Diagnostic biopsy 42.9% vs. 11.1%, n.s 33.3% vs. 16.7%, n.s
Preoperative KPS: 90‑100% 57.1% vs. 22.2%, n.s 66.7% vs. 33.3%, n.s
Postoperative KPS: 90‑100% 42.9% vs. 30.0%, n.s 66.7% vs. 30.8%, n.s
Preoperative seizures: yes 42.9% vs. 33.3%, n.s 66.7% vs. 25.0%, n.s
Eloquence: yes 57.1% vs. 66.7%, n.s 66.7% vs. 58.3%, n.s
*n.s: no significant; P > 0.05. KPNA2: karyopherin a2; KPS: karnofsky performance score

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