BACKGROUND Red blood cells (RBCs) can have a modulatory effect on immune cells; so changes in their dynamism could considerably influence their physiology, and consequently the immune activities of neighbouring cells, like natural killer (NK) cells. Herein, we studied the effect of both RBCs and lack of cell movement on the proliferation, survival and regulation of peripheral IL-2-stimulated NK cells from normal and solid malignant conditions. METHODS Experiments were conducted on twelve cell culture groups, including NK cells from patients with solid malignant tumor or healthy controls, cultured alone or with autologous or nonautologous RBCs under shaking or no shaking conditions. RESULTS NK cells from neoplastic patients behaved differently depending on the culture conditions including shaking and/or RBCs presence. Therefore, NK cells survival was downregulated in the absence of shaking; whereas, shaking have not only upregulated cell survival, but also downregulated the levels of p53-related apoptosis. Moreover, RBCs enhanced NK cells proliferation; while, this effect was modulated by shaking. Furthermore, RBCs can generate opposite effects on the production and modulation of protumoral or immunosuppressive cytokines, depending on the origin of NK cells, i.e., whether they derive from healthy or solid malignant tumor conditions. Finally, NK cells become able to express Foxp3 regulatory marker when combining three main conditions that include (i) treatment with high dose of IL-2, (ii) presence of RBCs, and (iii) absence of shaking. CONCLUSIONS Our outcomes showed for the first time that cell stagnation would be markedly involved in peripheral NK cell apoptosis, as well as in switching toward a regulatory phenotype-induced Foxp3. Cell movement may be one of ex vivo potential approaches in boosting the activities and survival of such cells during solid cancer.

中文翻译：

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细胞运动的缺乏会损害外周血源自实体癌的IL-2刺激的自然杀伤细胞的存活，并促进红细胞诱导其向调节表型的转换。

背景技术红细胞（RBC）可以对免疫细胞产生调节作用。因此它们的动态变化可能会极大地影响其生理机能，进而影响邻近细胞（如自然杀伤（NK）细胞）的免疫活性。在本文中，我们研究了红细胞和缺乏细胞运动对正常和实体恶性肿瘤周围IL-2刺激的NK细胞增殖，存活和调节的影响。方法在十二个细胞培养组中进行实验，包括来自患有实体恶性肿瘤或健康对照的患者的NK细胞，分别在摇动或不摇动条件下单独培养或与自体或非自体RBC一起培养。结果肿瘤患者的NK细胞的行为取决于培养条件，包括摇动和/或RBC存在。因此，在没有晃动的情况下，NK细胞的存活被下调；而摇动不仅上调了细胞存活，还下调了p53相关的细胞凋亡水平。此外，红细胞增强了NK细胞的增殖。同时，通过摇晃来调节这种效果。此外，取决于NK细胞的来源，即，它们是否源自健康或实体恶性肿瘤状况，RBC可对前列腺癌或免疫抑制性细胞因子的产生和调节产生相反的作用。最后，当结合以下三个主要条件时，NK细胞就能够表达Foxp3调节标记：（i）用高剂量的IL-2进行治疗；（ii）存在红细胞；以及（iii）不摇晃。结论我们的结果首次显示细胞停滞将明显参与外周NK细胞凋亡，以及转向调节性表型诱导的Foxp3。细胞移动可能是在实体癌期间增强此类细胞的活性和存活的离体潜在方法之一。