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转移性恶性黑色素瘤患者化疗免疫治疗后白细胞介素-2受体表达的研究。

Study of IL-2 receptor expression after chemoimmunotherapy in patients treated for metastatic malignant melanoma.

作者信息

Mouawad R, Ichen M, Rixe O, Benhammouda A, Vuillemin E, Weil M, Khayat D, Soubrane C

机构信息

Department of Medical Oncology, Salpetrière Hospital, Paris, France.

出版信息

Clin Exp Immunol. 1994 Sep;97(3):342-6. doi: 10.1111/j.1365-2249.1994.tb06092.x.

DOI:10.1111/j.1365-2249.1994.tb06092.x
PMID:8082289
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1534843/
Abstract

Using flow cytometry, cellular IL-2 receptors were studied before and following chemoimmunotherapy combination in 20 patients with metastatic malignant melanoma (MMM). Patients received cisplatin (100 mg/m2) at days 1 and 28, recombinant IL-2 by continuous infusion from days 3 to 6, 17 to 21, 31 to 34, and 45 to 49. Interferon-alpha (IFN-alpha) was given subcutaneously three times weekly. In terms of clinical response, we observed 55% objective response (complete: 15%). When pretreatment blood samples were compared with those of healthy donors, we did not observe any change in low (alpha chain) and high affinity receptor (alpha + beta) expression. In contrast, intermediate affinity p75 (beta chain) expression was decreased significantly (P < or = 0.0001) in MMM patients. During treatment, we found a dramatic increase of beta chain as well as high affinity (alpha + beta) expression in responding patients, as soon as IL-2 therapy began. Furthermore, the increase of beta chain expression was limited to natural killer (NK) cells (CD56+). In non-responding patients, on the other hand, increase of both receptors was seen only at day 31. These data suggest the involvement of beta chain expression in the mechanism of cell activation after chemoimmunotherapy. Moreover, this early beta chain expression is correlated with the clinical response to chemoimmunotherapy.

摘要

采用流式细胞术,对20例转移性恶性黑色素瘤(MMM)患者化疗免疫联合治疗前后的细胞白细胞介素-2受体进行了研究。患者在第1天和第28天接受顺铂(100mg/m²)治疗,从第3天至第6天、第17天至第21天、第31天至第34天以及第45天至第49天持续输注重组白细胞介素-2。α干扰素(IFN-α)每周皮下注射3次。在临床反应方面,我们观察到55%的客观缓解率(完全缓解:15%)。当将预处理血液样本与健康供体的样本进行比较时,我们未观察到低亲和力(α链)和高亲和力受体(α + β)表达有任何变化。相比之下,MMM患者中中等亲和力的p75(β链)表达显著降低(P≤0.0001)。在治疗期间,我们发现,一旦开始白细胞介素-2治疗,缓解患者的β链以及高亲和力(α + β)表达就会急剧增加。此外,β链表达的增加仅限于自然杀伤(NK)细胞(CD56+)。另一方面,在无反应的患者中,仅在第31天观察到两种受体的增加。这些数据表明β链表达参与了化疗免疫治疗后的细胞激活机制。此外,这种早期的β链表达与化疗免疫治疗的临床反应相关。

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Study of IL-2 receptor expression after chemoimmunotherapy in patients treated for metastatic malignant melanoma.转移性恶性黑色素瘤患者化疗免疫治疗后白细胞介素-2受体表达的研究。
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引用本文的文献

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Immunomodulation following chemotherapy.化疗后的免疫调节
Breast Cancer Res Treat. 1996;38(1):41-8. doi: 10.1007/BF01803782.

本文引用的文献

1
Follow up of soluble IL-2 receptor level in metastatic malignant melanoma patients treated by chemoimmunotherapy.接受化学免疫疗法治疗的转移性恶性黑色素瘤患者可溶性白细胞介素-2受体水平的随访
Clin Exp Immunol. 1994 Feb;95(2):232-6. doi: 10.1111/j.1365-2249.1994.tb06516.x.
2
Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma.顺铂、白细胞介素-2和干扰素α-2a序贯化学免疫疗法治疗转移性黑色素瘤。
J Clin Oncol. 1993 Nov;11(11):2173-80. doi: 10.1200/JCO.1993.11.11.2173.
3
Biological activity of recombinant human interleukin-2 produced in Escherichia coli.在大肠杆菌中产生的重组人白细胞介素-2的生物活性。
Science. 1984 Mar 30;223(4643):1412-4. doi: 10.1126/science.6367046.
4
Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro.可溶性白细胞介素2受体在体外从活化的人淋巴细胞中释放出来。
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Repetitive weekly cycles of interleukin-2. II. Clinical and immunologic effects of dose, schedule, and addition of indomethacin.
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6
The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells.p75肽是在大颗粒淋巴细胞上表达的白细胞介素2受体,负责这些细胞的白细胞介素2激活。
Proc Natl Acad Sci U S A. 1987 Aug;84(15):5394-8. doi: 10.1073/pnas.84.15.5394.
7
Interleukin 2 high-affinity receptor expression requires two distinct binding proteins.白细胞介素2高亲和力受体的表达需要两种不同的结合蛋白。
J Exp Med. 1987 Jan 1;165(1):223-38. doi: 10.1084/jem.165.1.223.
8
Immunotherapy of cancer using interleukin 2: current status and future prospects.使用白细胞介素-2进行癌症免疫治疗:现状与未来前景
Immunol Today. 1988 Feb;9(2):58-62. doi: 10.1016/0167-5699(88)91261-3.
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In vivo administration of purified human interleukin-2 to patients with cancer: development of interleukin-2 receptor positive cells and circulating soluble interleukin-2 receptors following interleukin-2 administration.
Cancer Res. 1987 Apr 15;47(8):2188-95.
10
The released interleukin 2 receptor binds interleukin 2 efficiently.释放的白细胞介素2受体能有效结合白细胞介素2。
J Immunol. 1986 Dec 15;137(12):3841-4.