白细胞介素-15增强人γδT细胞的增殖、刺激表型和抗肿瘤效应功能。
Interleukin-15 enhances the proliferation, stimulatory phenotype, and antitumor effector functions of human gamma delta T cells.
作者信息
Van Acker Heleen H, Anguille Sébastien, Willemen Yannick, Van den Bergh Johan M, Berneman Zwi N, Lion Eva, Smits Evelien L, Van Tendeloo Viggo F
机构信息
Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijkstraat 10, 2650, Edegem, Antwerp, Belgium.
Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium.
出版信息
J Hematol Oncol. 2016 Sep 29;9(1):101. doi: 10.1186/s13045-016-0329-3.
BACKGROUND
Adoptive immunotherapy is gaining momentum to fight malignancies, whereby γδ T cells have received recent attention as an alternative cell source as to natural killer cells and αβ T cells. The advent of γδ T cells is largely due to their ability to recognize and target tumor cells using both innate characteristic and T cell receptor (TCR)-mediated mechanisms, their capacity to enhance the generation of antigen-specific T cell responses, and their potential to be used in an autologous or allogeneic setting.
METHODS
In this study, we explored the beneficial effect of the immunostimulatory cytokine interleukin (IL)-15 on purified γδ T cells and its use as a stimulatory signal in the ex vivo expansion of γδ T cells for adoptive transfer. The expansion protocol was validated both with immune cells of healthy individuals and acute myeloid leukemia patients.
RESULTS
We report that the addition of IL-15 to γδ T cell cultures results in a more activated phenotype, a higher proliferative capacity, a more pronounced T helper 1 polarization, and an increased cytotoxic capacity of γδ T cells. Moreover γδ T cell expansion starting with peripheral blood mononuclear cells from healthy individuals and acute myeloid leukemia patients is boosted in the presence of IL-15, whereby the antitumor properties of the γδ T cells are strengthened as well.
CONCLUSIONS
Our results support the rationale to explore the use of IL-15 in clinical adoptive therapy protocols exploiting γδ T cells.
背景
过继性免疫疗法在对抗恶性肿瘤方面正日益受到关注，其中γδ T细胞作为自然杀伤细胞和αβ T细胞的替代细胞来源最近受到了关注。γδ T细胞的出现很大程度上归因于它们利用固有特性和T细胞受体（TCR）介导的机制识别和靶向肿瘤细胞的能力、增强抗原特异性T细胞反应产生的能力以及在自体或异体环境中使用的潜力。
方法
在本研究中，我们探讨了免疫刺激细胞因子白细胞介素（IL）-15对纯化的γδ T细胞的有益作用及其作为γδ T细胞体外扩增用于过继性转移的刺激信号的用途。该扩增方案在健康个体和急性髓系白血病患者的免疫细胞中均得到验证。
结果
我们报告，在γδ T细胞培养物中添加IL-15会导致γδ T细胞呈现更活化的表型、更高的增殖能力、更明显的辅助性T细胞1极化以及增加的细胞毒性能力。此外，在IL-15存在的情况下，从健康个体和急性髓系白血病患者的外周血单核细胞开始的γδ T细胞扩增得到增强，γδ T细胞的抗肿瘤特性也得到加强。
结论
我们的结果支持在利用γδ T细胞的临床过继性治疗方案中探索使用IL-15的基本原理。
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