本橋 新一郎

A unique lymphocyte lineage, the V alpha 14 NKT cells, expresses both NK1.1 and an invariant antigen receptor encoded by V alpha 14 and J alpha 281 gene segments. Va14 NKT cells play crucial roles in various immune responses, including autoimmune diseases, allergic reactions and anti-tumor immunity. V alpha 14 NKT cells were demonstrated to be essential for anti-tumor effect of IL-12 in vivo. Here, we report that adoptive transfer of IL-12-activated Va alpha 14 NKT cells prevents hepatic metastasis of B16 melanoma. The injection of large amounts of IL-2, IL-4, and IFN-gamma, which are cytokines produced by activated V alpha 14 NKT cells, exhibited no significant inhibition of the metastasis of this melanoma. The cells prepared from the liver of IL-12-injected mice expressed a potent cytotoxic activity on B16 melanoma cells in vitro. Although the adoptive transfer of IL-12-activated V alpha 14 NKT cells prevents hepatic metastasis of B16 melanoma, activated NK cells from IL-12-injected RAG-I-/- mice failed to inhibit the metastasis of this melanoma. Thus, the anti-tumor effect of IL-12 can be replaced by adoptive transfer of IL-12-activated Va14 NKT cells but not by IL-12-activated NK cells, suggesting a minor role of NK cells for the IL-12-mediated anti-tumor effect in this experimental system. Moreover, our studies have suggested the involvement of direct cytotoxic mechanisms rather than cytokine-mediated immune responses at the effector phase of the V alpha 14 NKT cell-mediated anti-tumor activity. (C) 2001 Wiley-Liss, Inc.

Purpose: The majority of lung carcinoma patients requiring resection have smoking habits prior to surgical treatment, and the correlation of smoking with postoperative complications is well known, However, few studies have investigated the correlation between long-term survival and cigarette smoking in patients with primary, resected lung carcinoma. We analyzed the relationship between clinical factors, including cigarette smoking before surgery, and 10-year survival in stage I nan-small-cell lung carcinoma (NSCLC). Patients and Methods: Cigarette smoking habit and other factors influencing either the overall survival or the disease-specific survival rates of patients with stage I primary, resected NSCLC were evaluated according to the Cox proportional hazards model using a total of 369 patients with stage I-NSCLC, Results: Comparison of the cause of death in patients with 30 or more pack-years and patients with less than 30 pack-years showed significant differences in the prevalence of recurrent disease and onset of nonmalignant disease, Multivariate analysis demonstrated significant correlations between overall survival and age and pack-years. Disease-specific survival showed significant correlations with age, tumor classification, and visceral pleural invasion. Conclusion: Smoking pack-years is an important clinical prognostic factor in evaluating overall long-term survival in patients with stage I primary, resected NSCLC. (C) 1999 by American Society of Clinical Oncology.

Elevated expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 have been implicated as playing important roles in tumor invasion and metastasis in various tissues. We investigated the relationship between circulating plasma MMP-9, its expression in tumor samples, and other clinical features in patients with non-small cell lung cancer (NSCLC), A series of 73 patients (45 men and 28 women) who underwent surgery for NSCLC was used in this study. Preoperative plasma concentrations of hlh;UP-9 were examined using a one-step sandwich enzyme immunoassay. Expression levels of MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were measured in 24 tumor samples by immunohistochemistry. The plasma concentration of MMP-9 in NSCLC patients (71.0 +/- 60.2 ng/ml) was significantly elevated compared to that of healthy volunteers (P < 0.0001), MMP-9 concentrations were elevated in 33 of 73 cases (45.2%), compared with a cutoff value of the mean +/- 2 SD in healthy volunteers. There were statistically significant differences in MMP-9 concentration in adenocarcinoma versus squamous cell carcinoma (P 0.014) and adenocarcinoma versus large cell carcinoma (P = 0.014), Five of 24 patients (20.8%) had positive immunohistochemical MMP staining of the tumor cell cytoplasm, and two cases had positive staining in the surrounding stromal cells. Plasma MMP-9 concentrations were elevated in 45.2% of NSCLC patients; however, this elevation did not seem to correlate with MMP-9 production by cancer and stromal cells. Ne concluded that the MMP-9 ELISA could be a beneficial adjunct for assessing the tumor burden of NSCLC, especially for types of squamous cell carcinoma and large cell carcinoma.

症例は26才男性で1992年11月左上腕の滑膜肉腫にて上腕の切断術を行った.術前術後化学療法を実施したが無効で翌年2月胸部CTにて異常陰影が認められ, 手術目的で同年7月当科に紹介された.入院時胸部CTにて両側肺野に多発性腫瘤陰影を認めた.入院後, 抗癌剤化学療法および開胸術4回施行するも, 効果なく, 1994年2月よりIL-2, LAK細胞による養子免疫療法を追加した.その後1997年4月までに3回の開胸術と化学療法に加えて18クールのIL-2, LAK療法を施行し, 4年後の現在健在である.養子免疫療法の副作用は主に発熱, 悪寒, 戦慄であるが2～3日で回復する.術後の化学療法を含めた養子免疫療法により再発までの期間の延長と転移数の減少が期待できると考えられた.