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肿瘤引流淋巴结中的自然杀伤细胞活性:对恶性黑色素瘤和头颈癌患者的研究

Natural killer cell activity in tumor-draining lymph nodes: investigations in patients with malignant melanoma and head and neck cancer.

作者信息

Micksche M, Vinzenz K, Kokoschka E M, Kokoschka R

出版信息

Nat Immun Cell Growth Regul. 1985;4(6):315-27.

PMID:4088287
Abstract

Mononuclear cells isolated from peripheral blood (PB) of patients with malignant melanoma and head and neck cancer were tested for natural killer (NK) cell activity against K562 targets. Significantly lower levels of NK activity were observed in patients with malignant melanoma with metastatic disease in comparison to stage I and control population. In head and neck cancer NK activity was normal in tumor stage 1-2 and significantly impaired in stage 3-4. Mononuclear cells (MNC) isolated from primary tumor-draining lymph nodes (LNs) had significant NK activity in 12 of 25 (48%) of melanoma and 9 of 19 (47%) of head and neck lymph nodes at E:T 40:1. Reactivity was always significantly lower than in autochthonous Preincubation (+37 degrees C, 18 h) of lymph node mononuclear cells (LNMNC) resulted in a significant increase in cytotoxicity in 36% of melanoma and 32% of head and neck LNs. Simultaneous incubation with interferon (IFN)-alpha resulted in 24% of melanoma and 44% of head and neck LNs in a significant further augmentation of NK activity. LNMNC were furthermore found to react in 2-24% (mean 7.79 +/- 2.1) with the monoclonal antibody HNK-1, which identifies a certain proportion of NK cells. No correlation was found between percentage HNK-1+ cells and the expression of NK activity. From these studies it may be concluded that tumor draining LNs contain cells which are active against K562 targets expressing low but variable levels of cytotoxicity. NK cell activity can be increased by incubation of LNMNC at 37 degrees C with or without addition of IFN. These results suggest that modulation of NK activity in tumor draining LNs might be achieved by local application of biological response modifiers, which might finally lead to an increase of local tumor defense mechanisms.

摘要

对从恶性黑色素瘤和头颈癌患者外周血(PB)中分离出的单核细胞进行检测,以观察其对K562靶细胞的自然杀伤(NK)细胞活性。与I期患者和对照组相比,有转移性疾病的恶性黑色素瘤患者的NK活性水平显著降低。在头颈癌中,1 - 2期肿瘤患者的NK活性正常,而3 - 4期患者的NK活性则显著受损。从原发性肿瘤引流淋巴结(LN)中分离出的单核细胞(MNC),在E:T为40:1时,25例黑色素瘤患者中有12例(48%)、19例头颈淋巴结中有9例(47%)具有显著的NK活性。其反应性总是显著低于自身外周血单核细胞。淋巴结单核细胞(LNMNC)在37℃预孵育18小时后,36%的黑色素瘤淋巴结和32%的头颈癌淋巴结的细胞毒性显著增加。与干扰素(IFN)-α同时孵育,可使24%的黑色素瘤淋巴结和44%的头颈癌淋巴结的NK活性进一步显著增强。此外,还发现LNMNC与单克隆抗体HNK - 1的反应率为2% - 24%(平均7.79±2.1),该抗体可识别一定比例的NK细胞。未发现HNK - 1 +细胞百分比与NK活性表达之间存在相关性。从这些研究中可以得出结论,肿瘤引流淋巴结中含有对表达低水平但可变细胞毒性的K562靶细胞具有活性的细胞。通过在37℃孵育LNMNC,无论是否添加IFN,均可增强NK细胞活性。这些结果表明,通过局部应用生物反应调节剂可能实现对肿瘤引流淋巴结中NK活性的调节,这最终可能导致局部肿瘤防御机制增强。

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