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




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BMC Medical Genomics

, 7:49

Bioinformatic and algorithmical studies

Abstract

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-2 and CIKIL-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.

ResultsThe results indicated that CIKIL-15 showed improved cell proliferation capacity compared to CIKIL-2. However, CIKIL-2 has exhibited greater tumor cytotoxic effect than CIKIL-15. Employing deep sequencing, we sequenced mRNA transcripts in CIKIL-2 and CIKIL-15. A total of 374 differentially expressed genes DEGs were identified including 175 up-regulated genes in CIKIL-15 and 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-2 through type I interferon signaling.

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

KeywordsCIK cells Interleukin 2 Interleukin 15 Deep sequencing Transcriptome Electronic supplementary materialThe online version of this article doi:10.1186-1755-8794-7-49 contains supplementary material, which is available to authorized users.

Wenju Wang, Mingyao Meng contributed equally to this work.

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Autor: Wenju Wang - Mingyao Meng - Yayong Zhang - Chuanyu Wei - Yanhua Xie - Lihong Jiang - Chunhui Wang - Fang Yang - Weiwei Ta

Fuente: https://link.springer.com/







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