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重组白细胞介素-2与淋巴因子激活的杀伤细胞治疗晚期膀胱癌:临床结果及免疫效应

Recombinant interleukin-2 and lymphokine-activated killer cell treatment of advanced bladder cancer: clinical results and immunological effects.

作者信息

Hermann G G, Geertsen P F, von der Maase H, Steven K, Andersen C, Hald T, Zeuthen J

机构信息

Department of Tumor Cell Biology, The Fibiger Institute, Danish Cancer Society, Copenhagen.

出版信息

Cancer Res. 1992 Feb 1;52(3):726-33.

PMID:1732060
Abstract

The purpose of this study was to evaluate the efficacy of treatment with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells in patients with advanced bladder cancer and to study the induced changes in the distribution of leukocyte subsets in blood and tumor. Nine patients with metastatic transitional cell cancer of the bladder were treated with a continuous infusion of rIL-2 combined with lymphocytes stimulated in vitro with rIL-2. None of the patients responded to the therapy despite substantial changes observed in the immunological cells, both in tumor and blood. The rIL-2 infusion induced migration of leukocytes to the tumors, which was related to increased expression of the adhesion molecule VLA-1 on both peripheral blood mononuclear cells and the endothelial cells of small tumor vessels. Only T-cells, predominately expressing IL-2 receptors, and macrophages infiltrated the tumors. Natural killer cells remained few or absent in the tumors, even though the natural killer cells in peripheral blood were activated by the treatment. This study shows that the present technique of rIL-2 and lymphokine-activated killer cell therapy is able to induce substantial changes in the immune system of patients with metastatic bladder cancer. However, this treatment did not induce tumor regression, which may be due to the advanced stage of disease.

摘要

本研究的目的是评估重组白细胞介素-2(rIL-2)和淋巴因子激活的杀伤细胞治疗晚期膀胱癌患者的疗效,并研究血液和肿瘤中白细胞亚群分布的诱导变化。9例转移性膀胱移行细胞癌患者接受了持续输注rIL-2联合体外经rIL-2刺激的淋巴细胞治疗。尽管在肿瘤和血液中的免疫细胞中观察到了显著变化,但没有患者对该治疗有反应。rIL-2输注诱导白细胞向肿瘤迁移,这与外周血单个核细胞和小肿瘤血管内皮细胞上黏附分子VLA-1表达增加有关。只有主要表达IL-2受体的T细胞和巨噬细胞浸润肿瘤。尽管外周血中的自然杀伤细胞被该治疗激活,但肿瘤中的自然杀伤细胞仍然很少或不存在。本研究表明,目前的rIL-2和淋巴因子激活的杀伤细胞治疗技术能够在转移性膀胱癌患者的免疫系统中诱导显著变化。然而,这种治疗并未诱导肿瘤消退,这可能是由于疾病处于晚期。

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