Global transcriptome-wide analysis of CIK cells identify distinct roles of IL-2 and IL-15 in acquisition of cytotoxic capacity against tumor

BMC Medical Genomics

Ruhong Li¹  Zongliu Hou¹  Jie Zong³  Dai Chen³  Xingfang Jin¹  Weiwei Tang¹  Fang Yang²  Chunhui Wang¹  Lihong Jiang¹  Yanhua Xie¹  Chuanyu Wei¹  Yayong Zhang¹  Mingyao Meng¹  Wenju Wang¹ 

[1] Yan’an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People’s Republic of China;Kunming Medical University, Kunming 650050, Yunnan, People’s Republic of China;Novel Bioinformatics Co., Ltd, Shanghai, China

关键词: Transcriptome;    Deep sequencing;    Interleukin 15;    Interleukin 2;    CIK cells;   

Others  :  1090633
DOI  :  10.1186/1755-8794-7-49

 received in 2014-04-09, accepted in 2014-08-05,  发布年份 2014

【 摘 要 】

Background

Cytokine-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.

Methods

CIK_IL-2 and CIK_IL-15 were 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.

Results

The results indicated that CIK_IL-15 showed improved cell proliferation capacity compared to CIK_IL-2. However, CIK_IL-2 has exhibited greater tumor cytotoxic effect than CIK_IL-15. Employing deep sequencing, we sequenced mRNA transcripts in CIK_IL-2 and CIK_IL-15. A total of 374 differentially expressed genes (DEGs) were identified including 175 up-regulated genes in CIK_IL-15 and 199 up-regulated genes in CIK_IL-2. Among DEGs in CIK_IL-15, Wnt signaling and cell adhesion were significant GO terms and pathways which related with their functions. In CIK_IL-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 CIK_IL-15, while inhibitory signal from interaction between CTLA4 and CD80 may be responsible for the weak proliferation capacity of CIK_IL-2. Moreover, up-regulated expressions of CD40LG and IRF7 may make for improved tumor cytolytic function of CIK_IL-2 through type I interferon signaling.

Conclusions

Through our findings, we have preliminarily elucidated the cells proliferation and acquisition of tumor cytotoxicity mechanism of CIK_IL-15 and CIK_IL-2. Better understanding of these mechanisms will help to generate novel CIK cells with greater proliferation potential and improved tumor cytolytic function.

【 授权许可】

   
2014 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

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