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乳腺癌的家族性发病与自然杀伤细胞细胞毒性降低有关。

Familial occurrence of breast cancer is associated with reduced natural killer cytotoxicity.

作者信息

Strayer D R, Carter W A, Brodsky I

出版信息

Breast Cancer Res Treat. 1986;7(3):187-92. doi: 10.1007/BF01806249.

DOI:10.1007/BF01806249
PMID:3779116
Abstract

A factor in the incidence of spontaneous neoplasms in mice is the endogenous level of natural cell-mediated cytotoxicity. These immunosurveillant or host defense mechanisms are probably under the control of multiple gene products including interferons. We studied natural killer (NK) cytotoxicity using peripheral blood mononuclear cells from 59 normal individuals with either a high (17) or low (42) familial incidence of breast cancer. The K562 cell line was used as target in 51Cr release assays. Three effector: target ratios (6.2:1, 25:1, and 50:1) were studied in quadruplicate using 3, 4 and 5-h incubations. Significantly lower natural killer activity (p less than 0.002) was detected in normal individuals with high familial incidences of breast cancer compared to individuals with low incidences in each of the three separate assays (50:1). The same conclusion was reached whether the data were expressed in terms of lytic units per 10(7) blood mononuclear cells or as % specific 51Cr released. Thus, a relationship was observed between the occurrence of breast cancer in closely related family members and low natural cell-mediated cytotoxicity. This result suggests that defects in NK activity may play a role in the initiation of human breast tumors. However, prospective studies will be necessary to establish whether low NK cell activity is a risk factor for breast cancer.

摘要

小鼠自发性肿瘤发生率的一个因素是天然细胞介导的细胞毒性的内源性水平。这些免疫监视或宿主防御机制可能受包括干扰素在内的多种基因产物的控制。我们使用来自59名正常个体的外周血单核细胞研究了自然杀伤(NK)细胞毒性,这些个体中乳腺癌家族发病率高的有17人,低的有42人。在51Cr释放试验中,K562细胞系用作靶细胞。使用3、4和5小时的孵育时间,对三种效应细胞与靶细胞比例(6.2:1、25:1和50:1)进行了一式四份的研究。在三项独立试验(50:1)的每一项中,与乳腺癌家族发病率低的个体相比,乳腺癌家族发病率高的正常个体检测到的自然杀伤活性显著降低(p<0.002)。无论数据是以每10(7)个血液单核细胞的裂解单位表示还是以特异性51Cr释放的百分比表示,都得出了相同的结论。因此,观察到密切相关家庭成员中乳腺癌的发生与低天然细胞介导的细胞毒性之间存在关联。这一结果表明,NK活性缺陷可能在人类乳腺肿瘤的发生中起作用。然而,需要进行前瞻性研究来确定低NK细胞活性是否是乳腺癌的一个危险因素。

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J Clin Invest. 1983 May;71(5):1230-9. doi: 10.1172/jci110872.

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本文引用的文献

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MHC Class I Deficiency in Solid Tumors and Therapeutic Strategies to Overcome It.MHC Ⅰ类分子缺陷与实体瘤及克服策略
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Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk.相同的 HLA-C2 和 Bw4 配体上抑制性和激活型杀伤细胞免疫球蛋白样受体的共存赋予乳腺癌风险。
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The Peripheral Immune Landscape of Breast Cancer: Clinical Findings and In Vitro Models for Biomarker Discovery.乳腺癌的外周免疫格局:生物标志物发现的临床研究结果及体外模型
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Association of Germline Variants in Natural Killer Cells With Tumor Immune Microenvironment Subtypes, Tumor-Infiltrating Lymphocytes, Immunotherapy Response, Clinical Outcomes, and Cancer Risk.自然杀伤细胞种系变异与肿瘤免疫微环境亚型、肿瘤浸润淋巴细胞、免疫治疗反应、临床结局和癌症风险的关联。
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Breast Cancer Res Treat. 1984;4(2):109-16. doi: 10.1007/BF01806393.
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7
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Nature. 1980 Apr 10;284(5756):553-5. doi: 10.1038/284553a0.
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Int J Cancer. 1981 Mar 15;27(3):321-7. doi: 10.1002/ijc.2910270310.
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Murine NK cell cultures: effects of interleukin-2 and interferon on cell growth and cytotoxic reactivity.小鼠自然杀伤细胞培养:白细胞介素-2和干扰素对细胞生长及细胞毒性反应性的影响
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