Dynamically expressed microRNA-15b modulates the activities of CD8 + T lymphocytes in mice with Lewis lung carcinoma
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RESEARCH
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Dynamically expressed microRNA-15b modulates the activities of CD8+ T lymphocytes in mice with Lewis lung carcinoma Guocheng Zhong1, Xiaoming Cheng2, Haixia Long1, Luhang He1, Wei Qi1, Tong Xiang1, Zhongquan Zhao1 and Bo Zhu1*
Abstract Background: CD8+ T cells are key members of adaptive immunity against tumorigenesis. As subset of CD8+ T cells, effector T cells (Te) and memory T cells (Tm) have different biological activities. The former can kill tumor cells but come into apoptosis in a certain period and the latter is static with the ability of self-renewal. Previous studies showed that microRNAs (miRNA) played critical roles in regulating adaptive immunity. This study aimed to identify the different expression of miRNAs between Te and Tm cells in tumor-bearing mice and to sort out the target miRNAs which can be regulated to improve anti-tumor activities of CD8+ T cells. Methods: miRNA expression profiling was performed on CD8+ Te and Tm cells from mice with Lewis lung carcinoma. Differentially expressed miRNA (miRNA-15b) was chosen and analyzed by qRT-PCR. Then, flow cytometry, ELISA, and CFSE kit were used to evaluate the biological effects of miRNA-15b on apoptosis, cytokine secretion, phenotype, and proliferation of CD8+ T cell. The possible downstream target genes of this miRNA were also analyzed. Results: Analysis of miRNA microarray and qRT-PCR showed that the level of miRNA-15b was higher in CD8+ Tm cells than in Te cells. Higher expression of miRNA-15b was observed in CD8+ T cells from tumor-bearing mice than those from healthy ones. Transfection of CD8+ T cells with miRNA-15b mimics could prevent T cells from apoptosis by inhibiting the translation of DEDD (Death Effector Domain-containing DNA binding protein). Moreover, ectopic miRNA-15b could inhibit the activation of CD8+ T cells (via repressing the production of IL-2 and IFN-γ and expression of CD69) and promote expression of CD44 through unknown pathways. Conclusion: Up-regulation of miRNA-15b in tumor environment might negatively regulate anti-tumor immunity through inhibiting function of CD8+ T cells. miRNA-15b might be a potential therapeutic target for immunotherapy. Keywords: microRNA-15b, CD8+ T lymphocyte, Immune function, Memory T cell
Background Cancer is a lethal disease with severe functional deterioration and high mortality. Currently, T cells, particularly CD8+ T cells have been widely employed as effector cells in anti-tumor immunotherapy [1,2]. However, the clinical efficacy of T cell immunotherapy is very limited because of the short lifetime of effector T cells due to their susceptibility to apoptosis in vivo. In addition, anti* Correspondence: [email protected] 1 Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People’s Republic of China Full list of author information is available at the end of the article
tumor activities of T cells are frequently impaired by powerful tumor microenvironments [3]. Therefore, it has attracted many researchers to explore
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