Monocyte-derived microparticles may be a sign of vascular complication in patients with lung cancer.

We measured and compared the levels of plasma monocyte-derived microparticles (MDMP) and platelet activation markers [plasma platelet-derived microparticles (PDMP), CD62P binding to platelets; plt-CD62P, CD63 binding to platelets; plt-CD63], to develop a better understanding of their potential contribution to vascular complications of lung cancer. The concentrations of MDMP and PDMP in lung cancer patients were significantly higher (P < 0.01) than those in normal subjects. Levels of plt-CD62P and plt-CD63 were significantly higher (P < 0.001 for each) in lung cancer patients than in controls. Levels of sE-selectin were also higher in lung cancer patients than in control subjects. MDMP correlated positively with plt-CD62P, plt-CD63, and PDMP with its relation to PDMP being particularly significant. The number of MDMPs and PDMPs are patients who are non-small cell lung cancer were significantly higher than that in small cell lung cancer patients. In addition, levels of sE-selectin were higher in non-small cell lung cancer than in small cell lung cancer patients. These findings suggest that elevated MDMPs may be a sign of vascular complication in lung cancer patients, particularly those who suffer from non-small cell lung cancer.

Comparison of interleukin-12 with lung cancer and malignant lymphoma undergoing autologous peripheral blood stem cell transplantation.

PURPOSE: High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for solid tumors including lung cancer. METHODS: We measured IL-12 levels in patients with lung cancer undergoing autologous PBSCT in order to elucidate the role of IL-12 in immune response recovery following stem cell transplantation. RESULTS: Compared to IL-12 levels at 1 week after PBSCT for lung cancer patients, those at 3 weeks were significantly increased ( P<0.01). In contrast, serum IL-12 levels in malignant lymphoma patients did not change significantly. There were no significant differences in levels of other cytokines between 1 week and 3 weeks after transplantation in patients with lung cancer. The frequency of helper/inducer T cells was increased in peripheral blood 1 week after transplantation in both lung cancer and malignant lymphoma patients. There was a significant increase in activated T cell numbers following PBSCT. Furthermore, high levels of other activated T cells persisted in the post-PBSCT period in patients with lung cancer and the number of cytotoxic T cells significantly increased. Natural killer (NK) cell numbers also tended to increase, although that of malignant lymphoma was not significant. A strong correlation was observed between serum IL-12 levels and NK cell numbers and interferon-gamma levels in lung cancer not but in malignant lymphoma patients. The analysis of transfused PBSC showed that the numbers of granulocyte/macrophage colony-forming units were similar in lung cancer and malignant lymphoma patients. However, the number of CD34+ cells was significantly higher in lung cancer than in malignant lymphoma patients. All of the CD34+ subpopulations were lower in percentage in patients with lung cancer than in patients with malignant lymphoma. In particular, the CD34+ CD33- subpopulation was significantly lower in percentage in lung cancer patients. CONCLUSION: Our findings suggest that PBSC in lung cancer are potent mediators of anticancer activity and that they might play an immunotherapeutic role against autologous malignant cells.

Analysis of cytotoxic T lymphocytes and Fas/FasL in Japanese patients with non-small cell lung cancer associated with HLA-A2.

PURPOSE: In recent years, the use of immunotherapy for malignant tumors has been proposed. To explore the significance of immunotherapy for lung cancer, we examined two systems : the HLA class I and cancer-reactive CTL system, and the Fas-FasL system. METHODS: HLA class I (HLA-A, -B, and -C) antigens were determined in 61 patients with lung cancer and in 30 healthy controls. The HLA class I phenotype was investigated by serological techniques. HLA-A2 alleles were investigated by polymerase chain reaction sequence-specific primer analysis. We analyzed lymphocytes isolated from 61 patients with two-color surface labeling and flow cytometry. Furthermore, we analyzed sFas and sFasL expression by enzyme-linked immunosorbent assay (ELISA). We also examined lung cancer cell line-induced apoptosis of CD8(+) lymphocytes using confocal laser scanning microscopy. RESULTS: The HLA-A2 allele was observed in 27 of 61 patients with lung cancer. There were no differences in HLA-A2 allele classifications between lung cancer patients and controls. Thirty-six of the 61 lung cancer patients (57%) had elevated levels of sFas, and 16 of the 61 patients (26.2%) had elevated levels of sFasL. The sFas level of lung cancers with HLA-A2 was significantly higher than that of cancers without HLA-A2 ( P<0.01). This tendency was observed in every lung cancer tissue type, and the sFas levels of lung cancers with HLA-A2 associated significantly with the CTL levels of lung cancers with HLA-A2. Furthermore, compared to lung cancers without HLA-A2, CD8(+) T-cell levels were elevated in lung cancers with HLA-A2. In contrast, sFas levels of non-small cell lung cancers without HLA-A2 were higher than those in lung cancers with HLA-A2. In an in vitro experiment using lung cancer cell lines, we observed apoptosis of CD8(+) lymphocytes induced by lung cancer cells. Lung cancer-reactive CTLs are mobilized easily by restriction of HLA-A2, but this restriction is not always specific. In addition, FasL derived from lung cancer cells can induce apoptosis of CD8(+) T-cells, and the frequency of this phenomenon is increased in small cell lung cancers without HLA-A2. CONCLUSION: Our findings suggest that the effect of immunotherapy may be insufficient for non-small cell lung cancer without HLA-A2.