IL-23, a cytokine, which is composed of the p40 subunit shared with IL-12 and the IL-23-specific p19 subunit, has been shown to preferentially act on Th1 effector/memory CD4+ T cells and to induce their proliferation and IFN-γ production. The IL-23 is also reported to act on Th17-CD4+ T cells, which are involved in inducing tissue injury. In this study, we examined the antitumor effects associated with systemic administration of IL-23 and their mechanisms in mouse tumor system. Systemic administration of high-dose IL-23 was achieved using in vivo electroporation of IL-23 plasmid DNA into the pretibial muscles of C57BL/6 mice. The IL-23 treatment was associated with significant suppression of the growth of pre-existing MCA205 fibrosarcoma and prolongation of the survival of treated mice without significant toxicity when compared with those of the mice treated with EGFP. Although the therapeutic outcomes were similar to those with the IL-12 treatment, the IL-23 treatment induced characteristic immune responses distinctive to those of IL-12 treatment. The IL-23 administration even at the therapeutic levels did not induce detectable IFN-γ concentration in the serum. In vivo depletion of CD4+ T cells, CD8+ T cells, or NK cells significantly inhibited the antitumor effects of IL-23. Furthermore, the CD4+ T cells in the lymph nodes in the IL-23-treated mice showed significant IFN-γ and IL-17 response upon anti-CD3 mAb stimulation in vitro. These results and the ones in the IFN-γ or IL-12 gene knockout mice suggest that potent antitumor effects of IL-23 treatment could be achieved when the Th1-type response is fully promoted in the presence of endogenously expressed IL-12.

The carcinoembryonic antigen glypican-3 (GPC3) is a good target of anticancer immunotherapy against pediatric solid tumors expressing GPC3. In this non-randomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3-peptide vaccination in patients with pediatric solid tumors. Eighteen patients with pediatric solid tumors expressing GPC3 underwent GPC3-peptide vaccination (intradermal injections every 2 weeks), with the primary endpoint being the safety of GPC3-peptide vaccination and the secondary endpoints being immune response, as measured by interferon (IFN)-γ enzyme-linked immunospot assay and Dextramer staining, and the clinical outcomes of tumor response, progression free survival (PFS), and overall survival (OS). Our findings indicated that GPC3 vaccination was well tolerated. We observed disease-control rates [complete response (CR)+partial response+stable disease] of 66.7% after 2 months, and although patients in the progression group unable to induce GPC3-peptide-specific cytotoxic T lymphocytes (CTLs) received poor prognoses, patients in the partial-remission and remission groups or those with hepatoblastoma received good prognoses. The GPC3-peptide vaccine induced a GPC3-specific CTL response in seven patients, with PFS and OS significantly longer in patients with high GPC3-specific CTL frequencies than in those with low frequencies. Furthermore, we established GPC3-peptide-specific CTL clones from a resected-recurrent tumor from one patient, with these cells exhibiting GPC3-peptide-specific cytokine secretion. The results of this trial demonstrated that the GPC3-peptide-specific CTLs induced by the GPC3-peptide vaccine infiltrated tumor tissue, and use of the GPC3-peptide vaccine might prevent the recurrence of pediatric solid tumors, especially hepatoblastomas, after a second CR.

Endocrine pancreatic insufficiency after PPPD may be explainable by obstructive pancreatitis after operation. Taking together the results of pancreatic endocrine function and morphological changes of pancreatic remnant after PPPD, tumor enucleation should be considered as surgical approach in children with pancreas head tumor whenever possible.

The management of patients with acute perforated appendicitis with abscess is controversial. The aim of the present study was to assess the outcomes of treatment in patients with this condition. We retrospectively analyzed 31 patients (16 men and 15 women with a mean age of 8.4 years) with appendicitis presenting with abscess. Patients were divided into two groups (emergency operation group and interval operation group), and clinical characteristics and outcomes of treatment were investigated. On presentation, no differences in gender, age, body weight, duration of symptoms, temperature, white blood cell count, C-reactive protein level, or maximum size of the abscess in the axial view were detected between the two groups. Fifteen patients (48.4 %) underwent emergency surgery. The remaining 16 patients (51.6 %) were initially treated conservatively with antibiotics. All 16 patients underwent planned operations after receiving conservative treatment, and two (12.5 %) of these patients underwent appendectomy before the planned operation day because of recurrent appendicitis without abscess. There were no differences in the length of hospital stay. In the emergency operation group, six (40 %) patients presented with wound infection and four (26.7 %) developed a postoperative intra-abdominal abscess. No infective complications were reported in the interval operation group. Interval appendectomy after conservative treatment of pediatric ruptured appendicitis with abscess significantly reduced postoperative infection rates.