Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth

Yin, Yuan; Cai, Xing Fu; Chen, Xi; Liang, Hongwei; Zhang, Yujing; Li, Jing; Wang, Zuoyun; Chen, Xiu-Lan; Zhang, Wen; Yokoyama, Seiji; Wang, Cheng; Li, Liang; Liu, Limin; Hou, De‐Xing; Dong, Lei; Xu, Tao; Hiroi, Takachika; Yang, Fuquan; Ji, Hongbin; Zhang, Junfeng; Zen, Ke; Zhang, Chenyu

doi:10.1038/cr.2014.121

Cited by 232 publications

(207 citation statements)

References 46 publications

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“…Promyelocytic leukemia protein depletion increased SMAD 1/5/8 signaling and suppressing SMAD 2/3 signaling (see Figure 2), which promoted endothelial cell migration and tube formation. Similarly, the exchange of miRNAs from tumor cells to immune cells has been investigated [96][97][98]. miRNAs can also be transferred from stromal cells to tumor cells.…”

Section: Intra-and Intercellular Regulation Of Stromal Cells By Mirnasmentioning

confidence: 99%

Epigenetic control of the tumor microenvironment

2016

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Stromal cells of the tumor microenvironment have been shown to play important roles in both supporting and limiting cancer growth. The altered phenotype of tumorassociated stromal cells (fibroblasts, immune cells, endothelial cells etc.) is proposed to be mainly due to epigenetic dysregulation of gene expression; however, only limited studies have probed the roles of epigenetic mechanisms in the regulation of stromal cell function. We review recent studies demonstrating how specific epigenetic mechanisms (DNA methylation and histone post-translational modification-based gene expression regulation, and miRNA-mediated translational regulation) drive aspects of stromal cell phenotype, and discuss the implications of these findings for treatment of malignancies. We also summarize the effects of epigenetic mechanismtargeted drugs on stromal cells and discuss the consideration of the microenvironment response in attempts to use these drugs for cancer treatment.

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Section: Intra-and Intercellular Regulation Of Stromal Cells By Mirnasmentioning

confidence: 99%

Epigenetic control of the tumor microenvironment

2016

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“…49 Once secreted, tumor-derived miRNA-214 was transferred into T cells through exosomes, and then downregulated phosphatase and tensin homolog (PTEN) in T cells so as to promote Treg expansion. 57 Another study revealed that exosomes from lung cancer were rich in the EGFR. These exosomes induced tolerogenic DCs, which further facilitated Treg generation.…”

Section: Impairment Of Ctl Response and Induction Of Regulatory T Cellsmentioning

confidence: 99%

The exosomes in tumor immunity

2015

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Exosomes are a kind of nanometric membrane vesicles and can be released by almost all kinds of cells, including cancer cells. As the important mediators in intercellular communications, exosomes mediate exchange of protein and genetic material derived from parental cells. Emerging evidences show that exosomes secreted by either host cells or cancer cells are involved in tumor initiation, growth, invasion and metastasis. Moreover, communications between immune cells and cancer cells via exosomes play dual roles in modulating tumor immunity. In this review, we focus on exosome-mediated immunosuppression via inhibition of antitumor responses elicited by immune cells (DCs, NK cells, CD4 C and CD8 C T cells, etc.) and induction of immunosuppressive or regulatory cell populations (MDSCs, Tregs and Bregs). Transfer of cytokines, microRNAs (miRNAs) and functional mRNAs by tumor-derived exosomes (TEXs) is crucial in the immune escape. Furthermore, exosomes secreted from several kinds of immune cells (DCs, CD4 C and CD8 C Tregs) also participate in immunosuppression. On the other hand, we summarize the current application of DCderived and modified tumor-derived exosomes as tumor vaccines. The potential challenges about exosome-based vaccines for clinical application are also discussed.

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“…However, the immune system often fails to eliminate cancer cells. It has been demonstrated that tumour cells develop potent, overlapping mechanisms to foster immune privilege by including the infiltration of T regs into the tumour microenvironment [27][28][29][30]. T regs enriched in ovarian carcinoma lead to reduced survival [27] and this has also been observed in many other solid tumours, including melanomas, renal cancer, breast cancer, cervical cancer [31] and colorectal cancer [32].…”

Section: Introductionmentioning

confidence: 99%

Ovarian cancer stem cells promote tumour immune privilege and invasion via CCL5 and regulatory T cells

You

et al. 2017

Clinical and Experimental Immunology

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SummaryEmerging evidence indicates a link between the increased proportion of regulatory T cells (T regs ) and reduced survival in patients who have been diagnosed with cancer. Cancer stem cells (CSCs) have been indicated to play a vital role in tumour initiation, drug resistance and recurrence. However, the relationship between T regs and CSCs remains largely unknown. Here, we sorted out ovarian cancer stem-like side population (SP) cells and CD133 1 cells to investigate the influence of ovarian CSCs on T regs . Among the various immune-related molecules that we assessed, C-C motif chemokine ligand 5 (CCL5) was the most elevated in ovarian CSCs relative to that in the non-CSCs. The expression of its receptor, C-C motif chemokine receptor 5 (CCR5), was also increased on the surface of T regs in ovarian cancer patients. This receptor-ligand expression profile indicated that ovarian CSCs recruit T regs via CCL5-CCR5 interactions. We further assessed the expression of interleukin (IL)-10 in T regs cultured with different cancer cells. For the first time, to our knowledge, our findings describe the relationship between ovarian CSCs and T regs , and demonstrated that these two cell populations co-operate to promote tumour immune tolerance and enhance tumour progression.

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Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth

Cited by 232 publications

References 46 publications

Epigenetic control of the tumor microenvironment

Epigenetic control of the tumor microenvironment

The exosomes in tumor immunity

Ovarian cancer stem cells promote tumour immune privilege and invasion via CCL5 and regulatory T cells

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