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白细胞介素-12与接受自体外周血干细胞移植的肺癌和恶性淋巴瘤的比较。

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

作者信息

Yoshimura Chie, Nomura Shosaku, Kanazawa Shigenori, Kuwana Midori, Yamaguchi Kazuyuki, Fukuhara Shirou

机构信息

The First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi Osaka 570, Japan.

出版信息

J Cancer Res Clin Oncol. 2002 Jan;128(1):29-36. doi: 10.1007/s004320100270. Epub 2001 Nov 1.

Abstract

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.

摘要

目的

高剂量化疗联合外周血干细胞移植(PBSCT)已成为包括肺癌在内的实体瘤的重要治疗方法。

方法

我们检测了接受自体PBSCT的肺癌患者的白细胞介素-12(IL-12)水平,以阐明IL-12在干细胞移植后免疫反应恢复中的作用。

结果

与肺癌患者PBSCT后1周的IL-12水平相比,3周时的水平显著升高(P<0.01)。相比之下,恶性淋巴瘤患者的血清IL-12水平没有显著变化。肺癌患者移植后1周和3周之间其他细胞因子水平没有显著差异。肺癌和恶性淋巴瘤患者移植后1周外周血中辅助/诱导性T细胞频率均增加。PBSCT后活化T细胞数量显著增加。此外,肺癌患者PBSCT后其他活化T细胞高水平持续存在,细胞毒性T细胞数量显著增加。自然杀伤(NK)细胞数量也有增加趋势,尽管恶性淋巴瘤患者不显著。在肺癌患者中观察到血清IL-12水平与NK细胞数量及干扰素-γ水平之间有很强的相关性,但在恶性淋巴瘤患者中未观察到。对输注的外周血干细胞分析显示,肺癌和恶性淋巴瘤患者的粒细胞/巨噬细胞集落形成单位数量相似。然而,肺癌患者的CD34+细胞数量显著高于恶性淋巴瘤患者。肺癌患者所有CD34+亚群的百分比均低于恶性淋巴瘤患者。特别是,肺癌患者CD34+ CD33-亚群的百分比显著更低。

结论

我们的研究结果表明,肺癌患者的外周血干细胞是抗癌活性的有效介质,它们可能对自体恶性细胞发挥免疫治疗作用。

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