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首页> 外文期刊>Journal of Surgical Research: Clinical and Laboratory Investigation >Impaired natural killer cell lysis in breast cancer patients with high levels of psychological stress is associated with altered expression of killer immunoglobin-like receptors.
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Impaired natural killer cell lysis in breast cancer patients with high levels of psychological stress is associated with altered expression of killer immunoglobin-like receptors.

机译:患有高度心理压力的乳腺癌患者的自然杀伤细胞裂解功能受损,与杀伤免疫球蛋白样受体的表达改变有关。

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BACKGROUND: We previously reported that cancer-related psychological stress is associated with reduced natural killer (NK) cell lysis. We hypothesized that reduced NK cell cytotoxicity in patients with increased levels of stress would correlate with alterations in the expression of inhibitory NK cell receptors (killer immunoglobulin-like receptors, or KIRs). The specific aim of this study was to examine KIR expression in patients with high or low levels of psychologic stress and correlate alterations in KIR expression with NK cell function. MATERIALS AND METHODS: Two hundred twenty-seven patients underwent baseline evaluation of cancer-related psychological stress and were randomized to psychosocial intervention versus observation. From this population, two groups were defined based on pretreatment measurements of NK lytic activity, stress levels, and the availability of cryopreserved peripheral blood mononuclear cells (PBMC). Group I (n=9) had low stress by the Impact of Events Scale (IES), and high NK cell lysis at the 50:1 effector: target ratio (NK(50)=52-89%). Group II (n=8) had high stress and low NK(50) (27-52%). Lymphokine activated killer (LAK) activity, antibody dependent cellular cytotoxicity (ADCC), and expression of cytokine receptors, adhesion molecules, and killer immunoglobulin-like receptors (KIRs) were assessed in PBMC. RESULTS: Incubation of PBMC with NK-stimulatory cytokines (IL-2, IL-12, or IL-15) led to significant increases in cytotoxic activity regardless of IES/NK(50) scores. There were no significant group differences in NK cell surface expression of the IL-2 receptor components CD25 and CD122, antibody-dependent lysis of HER2eu-positive SKBr3 cells treated with an anti-HER2eu monoclonal antibody, expression of adhesion molecules (CD2, CD11a, CD18) and markers of activation (CD69), or expression of the KIRs CD158a, NKG2a, NKB1, and CD161. However, levels of CD158b were significantly higher in Group I after incubation in media alone or with IL-2, and CD94 expression was significantly lower in Group I after incubation with IL-2. CONCLUSIONS: In this study of a small subset of breast cancer patients chosen from a previous clinical trial of psychosocial intervention for breast cancer, impaired NK lysis in breast cancer patients with high levels of psychological stress was associated with alterations in surface expression of killer immunoglobulin-like receptors. However, immune effectors retained the ability to lyse antibody-coated targets and to initiate lymphokine-activated killer activity, irrespective of stress levels or baseline NK(50).
机译:背景:我们以前报道癌症相关的心理压力与减少自然杀伤(NK)细胞裂解有关。我们假设应激水平升高的患者降低NK细胞的细胞毒性将与抑制性NK细胞受体(杀伤性免疫球蛋白样受体或KIRs)表达的改变有关。这项研究的具体目的是检查高或低心理压力患者的KIR表达,并将KIR表达的变化与NK细胞功能相关联。材料与方法:27例患者接受了与癌症相关的心理压力的基线评估,并随机分为心理社会干预与观察。根据该人群的NK裂解活性,应激水平和冷冻保存的外周血单个核细胞(PBMC)的治疗前测量值,将其分为两组。根据事件量表(IES)的影响,第一组(n = 9)的压力较低,效应子与目标比例为50:1时,NK细胞裂解率较高(NK(50)= 52-89%)。第二组(n = 8)具有高压力和低NK(50)(27-52%)。在PBMC中评估了淋巴因子激活的杀手(LAK)活性,抗体依赖性细胞毒性(ADCC)以及细胞因子受体,粘附分子和杀伤性免疫球蛋白样受体(KIR)的表达。结果:PBMC与NK刺激细胞因子(IL-2,IL-12或IL-15)孵育导致细胞毒性活性显着增加,无论IES / NK(50)得分如何。 IL-2受体成分CD25和CD122的NK细胞表面表达,用抗HER2 / neu单克隆抗体处理的HER2 / neu阳性SKBr3细胞的抗体依赖性裂解,粘附分子的表达( CD2,CD11a,CD18)和激活标记(CD69),或KIR CD158a,NKG2a,NKB1和CD161的表达。然而,单独在培养基中或与IL-2一起孵育后,I组中CD158b的水平显着升高,而与IL-2一起孵育后,I组中CD94的表达显着较低。结论:在这项研究中,从先前对乳腺癌进行社会心理干预的临床试验中选出的一小部分乳腺癌患者中,患有高心理压力的乳腺癌患者的NK裂解受损与杀手免疫球蛋白表面表达的改变有关。像受体。然而,无论压力水平或基线NK(50)如何,免疫效应子均具有溶解抗体包被的靶标并启动淋巴因子激活的杀伤活性的能力。

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