Laboratory for Experimental Immunology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
Immunol Res. 2012 Apr;52(1-2):139-56. doi: 10.1007/s12026-012-8285-7.
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.
自然杀伤（NK）细胞不仅在肿瘤免疫学和传染病领域，而且在免疫学的各个方面，如移植、自身免疫和过敏反应等领域，成为研究的课题。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，还包括研究这个淋巴细胞亚群中穿孔素的表达和调节。由于 NK 细胞的活性受其环境的影响，我们显示了其活性在临床分期上的依赖性，以及不同血清、Th1 细胞因子及其组合在乳腺癌、霍奇金病和非霍奇金淋巴瘤患者中的体外效应，特别是在代谢和细胞膜变化方面，通过外周血淋巴细胞自发释放乳酸脱氢酶（LDH）来评估，这导致了自然细胞毒性校正的 LDH 酶释放测定。通过对恶性肿瘤患者的长期免疫监测，我们还显示了 NK 细胞在化疗免疫治疗过程中的调节动力学。在我们最近的研究中，我们提供了 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，提供了一些 NK 细胞受体的基础和细胞因子诱导表达的参考值，无论是在疾病评估中，还是在恶性肿瘤患者细胞因子治疗期间的免疫监测中。此外，我们还提供了经批准用于免疫治疗的细胞因子 IFN 和 IL-2 对 NK 细胞活性的调节的新方面，涉及黑色素瘤和其他恶性肿瘤中新型激活（NKG2D 和 CD161）和抑制（CD158a 和 CD158b）受体特性以及 CD16-和 CD56 定义的 NK 细胞及其小免疫调节和大细胞毒性亚群中信号分子的改变，因为 NK 细胞介导的肿瘤细胞杀伤取决于刺激和抑制信号之间的平衡。
