The aim of this study was to assess the outcome of treatment with 2-chlorodeoxyadenosine (2-CdA) in pediatric patients with Langerhans cell histiocytosis (LCH) in Japan. We retrospectively identified 17 pediatric LCH patients treated with 2-CdA. All patients were refractory or reactivated cases who had been initially treated according to the JLSG-02 protocol of the Japan LCH study group. At initiation of 2-CdA therapy, 4 patients had primary refractory multisystem (MS) disease with risk organ (RO) involvement (MS+), 9 patients had reactivated MS disease [5 MS+ and 4 without RO involvement (MS-)], and the remaining 4 patients had refractory/reactivated multifocal bone disease (MFB). Treatment with 2-CdA (4-9 mg/m(2)/day) was administered on 2-5 consecutive days and repeated every 3-4 weeks for a period that ranged from 2 to 12 months. Four primary refractory patients were treated with 2-CdA combined with high dose of cytarabine. In MS+ patients, response to treatment was observed in 5 of the 9 patients. In MS-/MFB patients, 5 of the 8 patients showed response to treatment. In the patients who were primary refractory or had reactivation during initial chemotherapy, 4 of 10 patients showed good response. On the other hand, in the patients having reactivation while off therapy, 6 of 7 patients showed good response. These findings suggest that 2-CdA is effective for reactivated LCH while off therapy.

It is well known that trastuzumab (TTZ) is molecular target drug for breast cancer overexpressing human epidermal growth factor receptor 2 (HER2). Novel immunotherapy by human peripheral blood mononuclear cells (PBMCs) activated with TTZ were examined. Proliferation of lymphocytes after adding of TTZ was obtained. Furthermore, lymphocytes activated with TTZ inhibited growth of breast cancer cells in vitro. It is noteworthy that remarkably high cellular cytotoxicity in lymphocytes activated with TTZ compared with that of CD3-and lymphokine (interleukin (IL)2)-activated killer (CD3-LAK) cells commonly used in immunotherapy were revealed.Key words trastuzumab; immunotherapy; human epidermal growth factor receptor 2The human epidermal growth factor receptor 2 (HER2) is overexpressed in 20 to 30% of breast cancers, increasing the aggressiveness of the tumor. The trastuzumab (TTZ) that targets the extracellular domain of HER-2 has a remarkable antitumor effect and is currently used worldwide for the treatment of breast cancer patients overexpressing HER2.1,2) Although the mechanisms underlying the action of TTZ are still not fully understood, inhibitory effects of TTZ by cell cycle arrest in G1 and induction of apoptosis on the growth of HER2-positive breast cancer cells in vitro have been reported. 1,3) In addition, it has been reported that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in the antitumor activity of TTZ.3) The combination chemotherapy with TTZ has been shown to improve survival for women with HER2-overexpressing metastatic breast cancer patients. [4][5][6][7] On the other hand, immunotherapy using lymphocyte stimulated with immunomodulators such as cytokines was noted in cancer therapy as attractive approach, since there is no serious side effects in immunotherapy, and significant prolongation in survival and disease free period in group of immunotherapy compared with no-treatment group have been reported. 8,9) Although the TTZ inhibits growth of human breast cancer cells overexpressing HER2 in vitro, the immunological effects of TTZ for peripheral blood mononuclear cells (PBMCs) have not yet been reported.Yoshida et al. have studied metastasis mechanism of cancer cells 10,11) and for clinical applications of immunotherapy using CD3-and lymphokine (interleukin (IL)2)-activated killer (CD3-LAK) cells. On the other hand, Ueoka et al. have investigated inhibitory effects of hybrid liposomes 12,13) composed of phosphatidylcholine and polyoxyethylenealkyl ether on the growth of tumor cells in vitro, in vivo, and for clinical applications. [14][15][16] On the basis of these studies for cancer, we have tried to develop new immunotherapy using TTZ which is molecular target drug. In this study, we investigated the cellular cytotoxicity of lymphocytes activated with TTZ on growth of breast cancer cells in vitro.First, we examined viability of PBMCs treated with TTZ on the basis of WST-8 assay.17) The results are shown in Fig. 1. No change in the number of PBMCs after adding TTZ solu...

Background/Aim: Immune checkpoint inhibitors (ICIs) have dramatically changed the clinical outcomes of advanced tumours. However, biomarkers for monitoring immunological features during immunotherapy remain unclear, especially those in the peripheral blood, which are easily available. This study evaluated the usefulness of nCounter Analysis System in identifying immunological biomarkers in peripheral blood mononuclear cells (PBMCs) during ICI therapy. Patients and Methods: PBMCs from two patients who responded well to ICI therapy were used, and the expression levels of immune-related mRNA and extracellular proteins were analyzed. Results: Changes in the expression levels of 55 genes from pre-treatment to on-treatment were bioinformatically similar between the two cases. The expression levels of PD-1 were consistent with those by flow cytometry analysis, a reliable tool for monitoring various markers. Conclusion: The nCounter Analysis System may be a potent tool to simultaneously investigate genes and proteins on PBMCs as biomarkers during immunotherapy using a small amount of sample. Although cancer is still the second leading cause of death worldwide, advances in cancer biology and immunology 4517 This article is freely accessible online.