Global transcriptome-wide analysis of CIK cells identify distinct roles of IL-2 and IL-15 in acquisition of cytotoxic capacity against tumor.
Global transcriptome-wide analysis of CIK cells identify distinct roles of IL-2 and IL-15 in acquisition of cytotoxic capacity against tumor.
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CIK 细胞的全转录组分析确定了 IL-2 和 IL-15 在获得抗肿瘤细胞毒性能力中的不同作用。
DOI：
10.1186/1755-8794-7-49
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发表时间：
2014-08-09
影响因子：
2.7
通讯作者：
Li R
中科院分区：
文献类型：
--
作者：
Wang W;Meng M;Zhang Y;Wei C;Xie Y;Jiang L;Wang C;Yang F;Tang W;Jin X;Chen D;Zong J;Hou Z;Li R
细胞因子诱导的杀伤细胞（CIK细胞）是一种新兴的肿瘤治疗方法。我们的前期研究表明，IL-2和IL-15联合刺激CIK细胞，可提高其增殖能力和肿瘤细胞毒活性。方法用IFN-γ诱导人外周血单个核细胞（PBMC），分别用IL-2和IL-15联合OKT 3刺激CIK细胞增殖，获得CIK细胞杀伤肿瘤细胞的功能。RNA-seq进行鉴定差异表达的基因，和基因本体论和通路为基础的分析被用来确定不同的作用，IL-2和IL-15在CIK preparation.ResultsThe结果表明，CIKIL-15表现出提高细胞增殖能力相比，CIKIL-2。然而，CIKIL-2表现出比CIKIL-15更强的肿瘤细胞毒作用。采用深度测序，我们对CIKIL-2和CIKIL-15中的mRNA转录物进行了测序。共鉴定出374个差异表达基因（DEG），其中CIKIL-15上调基因175个，CIKIL-2上调基因199个。在CIKIL-15的DEG中，Wnt信号和细胞粘附是与其功能相关的重要GO术语和通路。在CIKIL-2中，I型干扰素信号传导和干扰素-细胞因子受体相互作用是重要的GO术语和途径。我们发现Wnt 4和PDGFD的上调可能有助于增强CIKIL-15的细胞增殖能力，而CTLA 4和CD 80之间相互作用的抑制信号可能是CIKIL-2的弱增殖能力的原因。结论CIKIL-15和CIKIL-2通过I型干扰素信号通路促进细胞增殖和获得肿瘤细胞毒作用的机制初步阐明。更好地了解这些机制将有助于产生新的CIK细胞具有更大的增殖潜力和改善肿瘤细胞溶解功能。
BackgroundCytokine-induced killer (CIK) cells are an emerging approach of cancer treatment. Our previous study have shown that CIK cells stimulated with combination of IL-2 and IL-15 displayed improved proliferation capacity and tumor cytotoxicity. However, the mechanisms of CIK cell proliferation and acquisition of cytolytic function against tumor induced by IL-2 and IL-15 have not been well elucidated yet.MethodsCIKIL-2and CIKIL-15were generated from peripheral blood mononuclear cells primed with IFN-γ, and stimulated with IL-2 and IL-15 in combination with OKT3 respectively. RNA-seq was performed to identify differentially expressed genes, and gene ontology and pathways based analysis were used to identify the distinct roles of IL-2 and IL-15 in CIK preparation.ResultsThe results indicated that CIKIL-15showed improved cell proliferation capacity compared to CIKIL-2. However, CIKIL-2has exhibited greater tumor cytotoxic effect than CIKIL-15. Employing deep sequencing, we sequenced mRNA transcripts in CIKIL-2and CIKIL-15. A total of 374 differentially expressed genes (DEGs) were identified including 175 up-regulated genes in CIKIL-15and 199 up-regulated genes in CIKIL-2. Among DEGs in CIKIL-15, Wnt signaling and cell adhesion were significant GO terms and pathways which related with their functions. In CIKIL-2, type I interferon signaling and cytokine-cytokine receptor interaction were significant GO terms and pathways. We found that the up-regulation of Wnt 4 and PDGFD may contribute to enhanced cell proliferation capacity of CIKIL-15, while inhibitory signal from interaction between CTLA4 and CD80 may be responsible for the weak proliferation capacity of CIKIL-2. Moreover, up-regulated expressions of CD40LG and IRF7 may make for improved tumor cytolytic function of CIKIL-2through type I interferon signaling.ConclusionsThrough our findings, we have preliminarily elucidated the cells proliferation and acquisition of tumor cytotoxicity mechanism of CIKIL-15and CIKIL-2. Better understanding of these mechanisms will help to generate novel CIK cells with greater proliferation potential and improved tumor cytolytic function.
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影响因子：
5.8
作者：
Pawitan, Y;Michiels, S;Ploner, A
通讯作者：
Ploner, A
影响因子：
5.8
作者：
Li, Caiyan;Li, Hongzhe
通讯作者：
Li, Hongzhe
影响因子：
3.7
作者：
Prieto, Carlos;Risueno, Alberto;Fontanillo, Celia;De Las Rivas, Javier
通讯作者：
De Las Rivas, Javier
NLRP4 通过泛素连接酶 DTX4 靶向激酶 TBK1 进行降解，从而负调节 I 型干扰素信号传导
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y