Endogenous and tumour-derived microRNAs regulate cross-presentation in dendritic cells and consequently cytotoxic T cell function

Kikete, Siambi; Chu, Xiaoqian; Wang, Li; Bian, Yuhong

doi:10.1007/s10616-016-9975-0

Cited by 14 publications

(10 citation statements)

References 113 publications

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“…DCs are antigen presenting cells capable of intaking and processing antigens and present the antigen peptide complex to CD4 + T cells (Helper T cells, Th) by the classical antigen presentation pathway forming MHC II-peptide complex. Addionally, they also present the antigen peptide complex to CD8 + T cells (cytotoxic T lymphocyte, CTL) by the cross presentation pathway forming MHC I-peptide complex 35 - 36 . M/CpG-ODN-TRP2-Lipo may also be able to activate T cells by cross-presentation, thus achieving antitumor effect.…”

Section: Discussionmentioning

confidence: 99%

The enhanced antitumor-specific immune response with mannose- and CpG-ODN-coated liposomes delivering TRP2 peptide

Lai

Duan

et al. 2018

Theranostics

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Purpose: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo.Methods: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2180-188 peptide as liposomal vaccine. M/CpG-ODN-TRP2-Lipo treatment was used to intendedly induce activation of DCs and antitumor- specific immune response in vivo.Results: Our results demonstrated in vitro that the prepared liposomal particles were efficiently taken up by DCs. This uptake led to an enhanced activation of DCs, as measured by the upregulation of MHC II, CD80, and CD86. Furthermore, M/CpG-ODN-TRP2-Lipo effectively inhibited the growth of implanted B16 melanoma and prolonged the survival of mice. This therapy significantly reduced the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells, while simultaneously increasing the number of activated T cells, tumor antigen-specific CD8+ cytotoxic T cells, and interferon-γ-producing cells. At the same time, it was found to suppress tumor angiogenesis and tumor cell proliferation, as well as up-regulate their apoptosis. Interestingly, MyD88-knockout mice had significantly shorter median survival times compared to wild-type mice following the administration of M/CpG-ODN-TRP2-Lipo.Conclusions: The results suggested that the antitumor activities of the vaccine partially rely on the Myd88 signaling pathway. Interestingly, compared to whole tumor cell lysate-based vaccine, M/CpG-ODN-TRP2-Lipo, tumor specific antigen peptide-based vaccine, improved survival of tumor-bearing mice as well as enhanced their antitumor responses. All in all, we describe a novel vaccine formulation, M/CpG-ODN-TRP2-Lipo, with the aim of improving antitumor responses by alleviating the immunosuppressive environment in tumors.

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Section: Discussionmentioning

confidence: 99%

The enhanced antitumor-specific immune response with mannose- and CpG-ODN-coated liposomes delivering TRP2 peptide

Lai

Duan

et al. 2018

Theranostics

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“…Mature DCs can effectively activate the initial T cells and maintain the central part of the immune response [141,142]. Tumor-derived and endogenous exosomal miRNAs can regulate cross-presentation in dendritic cells and with other immune cells, this exomsomal miRNAs-mediated intercellular communication may affect the maturation of DCs [143,144]. In pancreatic cancer, exosomal miR-212-3p targets MHC class II TF RFXAP resulting in reduced expression of HLA-DR, -DP, and -DQ molecules and thus interfering with the function of DCs cells [145,146].…”

Section: Promoting the Formation Of Immunosuppressive Environmentmentioning

confidence: 99%

Exosomal miRNAs in tumor microenvironment

Tan

Xia

et al. 2020

J Exp Clin Cancer Res

115

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Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of tumor cells, fibroblasts, endothelial cells, and immune cells, as well as non-cellular components, such as exosomes and cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, such as proteins, lipids and nucleic acids. Exosomes carry biologically active miRNAs to shuttle between tumor cells and TME, thereby affecting tumor development. Tumor-derived exosomal miRNAs induce matrix reprogramming in TME, creating a microenvironment that is conducive to tumor growth, metastasis, immune escape and chemotherapy resistance. In this review, we updated the role of exosomal miRNAs in the process of TME reshaping.

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“…Chronic lymphocytic leukaemia TEx can upregulate endogenous PD‐L1 expression in monocytes and macrophages by transfer of non‐coding Y RNAs, while TEx from breast, lung and skin cancer carry functional PD‐L1 molecules on their surface . TEx can also prevent DC maturation and their miRNA cargo can inhibit DC cross‐presenting capabilities to tumour‐specific CTLs, thus inducing APC dysfunction.…”

Section: Exosomes In Tumour Immune Evasionmentioning

confidence: 99%

Role of exosomes in tumour and transplant immune regulation

Lema

Burlingham

2019

Scand J Immunol

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Exosomes are a potent means for intercellular communication. However, exosomes have received intensive research focus in immunobiology only relatively recently.Because they transport proteins, lipids and genetic material between cells, they are especially suited to amplify their parental cell's message and overcome the physical constraints of cell-to-cell contact, that is exosome release gives cells the ability to alter distant, non-contiguous cells. As progress is made in this field, it has become increasingly obvious that exosomes are involved in most biological processes. In the immune system, exosomes are fundamental tools used by every immune cell type to fulfil its function and promote inflammation or tolerance. In this review, we first summarize key aspects of immune cell-specific exosomes and their functions. Then, we describe how exosomes have been shown to be indispensable orchestrators of the immune response in two immunological scenarios, namely transplant rejection or tolerance, and tumour evasion or initiation of anti-tumour immune responses.

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Endogenous and tumour-derived microRNAs regulate cross-presentation in dendritic cells and consequently cytotoxic T cell function

Cited by 14 publications

References 113 publications

The enhanced antitumor-specific immune response with mannose- and CpG-ODN-coated liposomes delivering TRP2 peptide

The enhanced antitumor-specific immune response with mannose- and CpG-ODN-coated liposomes delivering TRP2 peptide

Exosomal miRNAs in tumor microenvironment

Role of exosomes in tumour and transplant immune regulation

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