Investigation of NK cell function and their modulation in different malignancies
Investigation of NK cell function and their modulation in different malignancies
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DOI：
10.1007/s12026-012-8285-7
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发表时间：
2012-04-01
影响因子：
4.4
通讯作者：
Spuzic, Ivan
中科院分区：
文献类型：
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作者：
Konjevic, Gordana;Jurisic, Vladimir;Spuzic, Ivan
NK细胞不仅在肿瘤免疫学和感染性疾病领域，而且在免疫学的所有方面，如移植、自身免疫和超敏反应中，都已成为研究的主题。我们的早期研究除了研究实验动物和人类的NK细胞活性外，还包括研究该淋巴细胞亚群中穿孔素的表达和调节。由于NK细胞活性受其环境的影响，我们在乳腺癌、霍奇金病和非霍奇金淋巴瘤患者中显示了其活性的临床阶段依赖性损害和不同血清、Th 1细胞因子及其组合的体外作用，特别是通过乳酸脱氢酶（LDH）的自发释放评价外周血淋巴细胞的代谢和细胞膜变化这导致对天然细胞毒性的LDH酶释放测定的校正。通过对恶性肿瘤患者的长期免疫监测，我们还显示了化学免疫治疗期间NK细胞调节的动力学。在我们最近的研究中，我们给出了健康个体中NK功能和NK细胞受体表达的新家族的数据，这些数据可能有助于NK细胞分析，通过给出一些NK细胞受体的基础和马槟榔碱诱导的表达的参考值，用于疾病评估或恶性肿瘤患者细胞因子治疗期间的免疫监测。此外，我们给出了通过批准用于免疫治疗的细胞因子IFN和IL-2调节NK细胞活性的新方面，在黑色素瘤和其他恶性肿瘤中，（NKG 2D和CD 161）和抑制性（CD 158 a和CD 158 b）受体特征和CD 16-和CD 56-中的信号分子NK细胞及其在外周血和淋巴结中的小的免疫调节和大的细胞毒性亚群，因为NK细胞介导的肿瘤细胞杀伤取决于刺激性和抑制性信号传导之间的平衡。
NK cells have become a subject of investigation not only in the field of tumor immunology and infectious diseases, but also within all aspects of immunology, such as transplantation, autoimmunity, and hypersensitivity. Our early studies aside from investigating NK cell activity in experimental animals and humans included studies of perforin expression and modulation in this lymphocyte subset. As NK cell activity is modified by their environment, we showed clinical stage-dependent impairment of their activity and in vitro effect of different sera, Th1 cytokines, and their combination in breast cancer, Hodgkin's disease, and non-Hodgkin's lymphoma patients, especially with respect to metabolic and cell membrane changes of peripheral blood lymphocytes evaluated by spontaneous release of the enzyme lactate dehydrogenase (LDH) that led to the correction of the LDH enzyme release assay for natural cytotoxicity. By long-term immuno-monitoring of patients with malignancies, we also showed the kinetics of NK cell modulation during chemo-immunotherapy. In our more recent studies, we give data of NK function and novel families of NK cell receptor expression in healthy individuals that may be of help in NK cell profiling, by giving referent values of basic and cytokine-induced expression of some NK cell receptors either in evaluation of disease or in immuno-monitoring during cytokine therapy of patients with malignancies. Moreover, we give novel aspects of modulation of NK cell activity by cytokines approved for immunotherapy, IFN and IL-2, in melanoma and other malignancies with respect to alterations in new activating (NKG2D and CD161) and inhibitory (CD158a and CD158b) receptor characteristics and signaling molecules in CD16- and CD56-defined NK cells and their small immunoregulatory and large cytotoxic subsets in peripheral blood and lymph nodes, as NK cell-mediated killing of tumor cells depends on the balance between stimulatory and inhibitory signaling.