Evasion of the immune system is often associated with malignant tumors. The cancer cell microenvironment plays an important role in tumor progression, but its mechanism is largely unknown. Here we show that an extracellular compound derived from gastric cancer (GC-EC) selectively suppresses CD161+CD3- natural killer (NK) cells. Splenocytes treated with GC-EC showed considerable proliferation and the CD161+CD3- NK cell population was time-dependently suppressed. Intracellular staining of IFN-γ was shown to be down-regulated in concert with granzyme B and perforin. A cytotoxicity assay of splenocytes treated with GC-EC against K-562 cells showed a significant reduction in cytolytic activity. Further, the immune-suppressive effect of GC-EC was more evident in a syngeneic tumor model in C57BL/6 mice. Animals treated with B16 F10 and GC-EC exhibited more aggravated tumor formation than animals treated with B16 F10 only. We demonstrated that inhibition of apoptosis while increasing PI3 K/AKT levels may provoke tumor formation by GC-EC. A cytokine array revealed the presence of several cytokines in GC-EC that negatively regulate immune cytolytic activity and could be potential candidates for immune-suppressive effects.

中文翻译：

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在同系小鼠模型中，胃癌细胞衍生的细胞外化合物抑制CD161 + CD3-淋巴细胞并加重肿瘤形成。

逃避免疫系统通常与恶性肿瘤有关。癌细胞微环境在肿瘤进展中起着重要作用，但其机制很大程度上未知。在这里，我们显示了一种源自胃癌（GC-EC）的细胞外化合物选择性抑制CD161 + CD3-自然杀伤（NK）细胞。用GC-EC处理的脾细胞显示出可观的增殖，并且CD161 + CD3-NK细胞群受到时间依赖性抑制。IFN-γ的细胞内染色显示与颗粒酶B和穿孔素一致下调。用GC-EC处理的脾细胞对K-562细胞的细胞毒性试验显示，细胞溶解活性显着降低。此外，在C57BL / 6小鼠的同基因肿瘤模型中，GC-EC的免疫抑制作用更加明显。与仅用B16 F10治疗的动物相比，用B16 F10和GC-EC治疗的动物表现出更大的恶性肿瘤形成。我们证明了在增加PI3 K / AKT水平的同时抑制细胞凋亡可能通过GC-EC引起肿瘤形成。细胞因子阵列揭示了GC-EC中存在几种细胞因子，这些细胞因子负调节免疫细胞溶解活性，并可能成为免疫抑制作用的潜在候选者。