Abstract | 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 CIKIL-15 showed improved cell proliferation capacity compared to CIK(IL-2). However, CIK(IL-2) has exhibited greater tumor cytotoxic effect than CIKIL-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.
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Authors | Wenju Wang, Mingyao Meng, Yayong Zhang, Chuanyu Wei, Yanhua Xie, Lihong Jiang, Chunhui Wang, Fang Yang, Weiwei Tang, Xingfang Jin, Dai Chen, Jie Zong, Zongliu Hou, Ruhong Li |
Journal | BMC medical genomics
(BMC Med Genomics)
Vol. 7
Pg. 49
(Aug 09 2014)
ISSN: 1755-8794 [Electronic] England |
PMID | 25108500
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Interleukin-15
- Interleukin-2
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Topics |
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cytokine-Induced Killer Cells
(cytology, drug effects, metabolism)
- Gene Expression Profiling
- Gene Ontology
- Gene Regulatory Networks
(drug effects)
- Humans
- Interleukin-15
(pharmacology)
- Interleukin-2
(pharmacology)
- Neoplasms
(genetics, immunology)
- Sequence Analysis, RNA
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