Analysis of cytokine and chemokine production by tumor cell lines including five lung cancers, a malignant mesothelioma, and a malignant melanoma recently established in our laboratory showed rather high production of IL-8 in all tumors and IL-6 in one lung cancer, the malignant mesothelioma, and the malignant melanoma. We investigated the migration of PBMCs to these tumor cells using Transwell plates and showed enrichment of Foxp3+ CD4 regulatory T cells (Tregs) in migrated T cells to both IL-6– and IL-8–producing tumors. Marked induction of CXCR1 expression on Foxp3+ CD4 Tregs by IL-6 followed by IL-8–mediated migration appeared to be responsible for enriched migration. Frequent production of IL-8 by the tumors and Treg migration to those tumors through induction of IL-8R expression by IL-6 is one of the mechanisms for tumor escape.

Serological analysis of a recombinant cDNA expression library (SEREX) derived from two lung adenocarcinoma cancer cell lines using autologous sera led to the isolation of 41 positive cDNA clones comprising 28 different antigens. They coded for a variety of nuclear and cytoplasmic proteins. Among the antigens, nucleoporin 107 (NUP107) was isolated most frequently (5 of 41 clones). The second most frequently isolated antigen was coded for by C21orf58 (4 of 41 clones). During serological analysis of selected antigens based on their reactivity to sera from normal individuals and lung cancer patients, none of the antigens showed a cancer-restricted recognition pattern. However, 5 genes including NUP107 showed higher expression when we examined the changes in gene expression in 5 different adenocarcinoma cell lines, including those used in SEREX, compared with their levels in normal lung tissues by cDNA microarray analysis. On the other hand, the expression levels of 5 genes including C21orf58 were down regulated in all adenocarcinoma cell lines. This SEREX study combining comprehensive gene expression assays has added to the growing list of lung cancer antigens, which may aid the development of diagnostic and immunotherapeutic reagents for patients with lung cancer.3

In high-resolution biopotential measurements, interference from local 60 Hz paver-line open disturbs the original signah so that it should be rejected as small as possible. The sources and elimination methods of this interference have been considered by many researchers. However, it does not completely eliminate because of many complex factors. We have designed a new method for eliminating the paver-line interference by using an automatic interference controller device (AICD). The principle of this method is based on automatically matching of the amplitude and the phase from power-line signal detector of AICD on those of interference of biopotential signaL In this work, we used ECG signal as one of biopotential signals source. The device does not make ECG signal distorted and only eliminates interference signal. Interference elimination can be performed continuously and rapidly even if the situations of interference are changing with time or frequency in electrical system are varied The handling is easy because of automatic system and it is applicable not only to ECG but also for the other biopotential signals.

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Background: Several mechanisms by which tumors evade the host immune response have been elucidated. A tumor modulates its antigenicity by immunoediting during development of an overt tumor, and frequently loses MHC and/or tumor antigen expression. Recently, it has been shown that regulatory T-cells were closely involved in immune impairment against tumors. Naturally occurring Foxp3+ CD25 high CD4 Tregs were observed in local tumor sites in some ovarian cancer patients and infiltration of those Tregs in the tumor correlated well with poor patient prognosis. Moreover, recently, an increase in the number of Tregs in the peripheral blood has been shown in advanced cancer patients and immune down-regulation systemically occurring in those patients is one cause of the ineffectiveness of immunization in clinical trials using cancer vaccines. The evidence suggests that it is necessary to regulate Tregs function and their accumulation to tumor local site for induction of effective immune response against tumors. Purpose: In this study, we investigated cytokine and chemokine production by tumor cell lines including 5 lung cancers, a malignant mesothelioma and a malignant melanoma recently established in our laboratory. We observed IL-8 production in all tumors and IL-6 production in one lung cancer, a malignant mesothelioma and a malignant melanoma. We investigated migration of Foxp3+ CD4 Tregs in PBMCs to those tumor cells using Transwell plates. Experimental Design: Cytokine and chemokine production was analyzed in tumor cell lines including 5 lung cancers, a malignant mesothelioma and a malignant melanoma recently established in our laboratory. IL-8 production was detected in all tumors and IL-6 production in 3 of them. We then investigated the role of IL-6 and IL-8 on migration of Foxp3+ CD4 Tregs to those tumor cells using Transwell plates. Induction of IL-8 receptor on Foxp3+ CD4 T-cells by IL-6 was investigated by flow cytometry and its role on their migration was examined by anti-IL-8R blocking. Results: We showed enrichment of Foxp3+ CD4 Tregs in migrated T-cells to both IL-6 and IL-8-producing tumors. Marked induction of CXCR1 (IL-8RA) expression was observed on Foxp3+ CD4 Tregs by the treatment with IL-6. Migration of IL-6-treated Foxp3+ CD4 T-cells to the tumors was blocked by the addition of anti-CXCR1. In fact, high level of IL-6 was detected in pleural effusion in most of lung cancer patients. Conclusions: Frequent production of IL-8 by the tumors and Treg migration to those tumors through induction of IL-8 receptor expression by IL-6 is one of the mechanisms for tumor escape. The findings indicate that the blocking of Treg migration by inhibiting IL-6-mediated IL-8 receptor expression could be a new strategy for tumor immunotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1915.