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低剂量环磷酰胺、白细胞介素-2和α-干扰素治疗后,反应性肾细胞癌患者的淋巴因子激活的杀伤细胞(LAK)和T细胞活化增强。

Increased LAK and T cell activation in responding renal cell carcinoma patients after low dose cyclophosphamide, IL-2 and alpha-IFN.

作者信息

Wersäll P, Mellstedt H

机构信息

Department of Oncology (Radiumhemmet), and Immunological Research Laboratory, Karolinska Hospital, Stockholm, Sweden.

出版信息

Med Oncol. 1995 Jun;12(2):69-77. doi: 10.1007/BF01676706.

Abstract

Immunologic monitoring of cancer patients treated with IL-2 might help to determine functions of significance for the clinical outcome. Some immune functions in patients with advanced renal cell carcinoma were studied during treatment with low dose cyclophosphamide, alpha-interferon and IL-2. Cyclophosphamide (500 mg m-2) was given day 1, and alpha-interferon (3 x 10(6) u i.m.) and continuous infusion of IL-2 (18 x 10(6) u m-2 day-1) for days 4-9. The cycle interval was 3 weeks. Two to six cycles were given. Eleven patients entered the study. One patient achieved a partial remission, two patients had a minor response and four had a stable disease ('responding patients'). NK cell activity (K562) increased in all patients while LAK cell activity (against a renal cell carcinoma cell line, A498) was significantly augmented only in responding patients. In the responder group, there was a significant increase in CD3+/HLA-DR+ T-cells. In parallel, there was a significant decrease in CD45RA+ cells as well as in the CD4/CD8 ratio. These data might indicate an expansion of activated T cells with a reduction of cells with a suppressor phenotype in responding patients. The results corroborate the importance of activation of LAK cells and T cells during IL-2 therapy of cancer patients.

摘要

对接受白细胞介素-2治疗的癌症患者进行免疫监测,可能有助于确定对临床结果具有重要意义的功能。在晚期肾细胞癌患者接受低剂量环磷酰胺、α-干扰素和白细胞介素-2治疗期间,对其一些免疫功能进行了研究。环磷酰胺(500mg/m²)于第1天给药,α-干扰素(3×10⁶单位,肌肉注射)和持续输注白细胞介素-2(18×10⁶单位/m²·天⁻¹)于第4至9天给药。周期间隔为3周。共给予2至6个周期。11名患者进入研究。1名患者实现部分缓解,2名患者有轻微反应,4名患者病情稳定(“有反应患者”)。所有患者的自然杀伤细胞活性(针对K562)均增加,而仅在有反应患者中,淋巴因子激活的杀伤细胞活性(针对肾癌细胞系A498)显著增强。在有反应组中,CD3⁺/HLA-DR⁺ T细胞显著增加。同时,CD45RA⁺细胞以及CD4/CD8比值显著降低。这些数据可能表明在有反应患者中,活化T细胞扩增,而具有抑制表型的细胞减少。结果证实了在癌症患者白细胞介素-2治疗期间激活淋巴因子激活的杀伤细胞和T细胞的重要性。

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