More efficient induction of antitumor T cell immunity by exosomes from CD40L gene-modified lung tumor cells

Wang, Jiaoli; Wang, Limin; Lin, Zifan; Tao, Lisha; Chen, Ming

doi:10.3892/mmr.2013.1759

Cited by 63 publications

(49 citation statements)

References 21 publications

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“…The isolated exosomes, verified by expression of exosome-specific markers TSG101, CD63, and HSP70 (Fig. 1b) [25–27], were added into hESC-derived cultures in exosome-depleted DM on day 6. As expected, we found that after 10-day treatment with A549-derived exosomes, but not with hiPSC-ATIIC- or hATIIC-derived exosomes, the hESC-derived SPC-expressing cells were enriched to the degree similar to that observed in hESC-derived cultures treated with A549-CM, suggesting an exosome-mediated communication between ATIICs (Fig.…”

Section: Resultsmentioning

confidence: 99%

Exosome miR-371b-5p promotes proliferation of lung alveolar progenitor type II cells by using PTEN to orchestrate the PI3K/Akt signaling

et al. 2017

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BackgroundPathways directing endogenous stem/progenitor cells to restore normal architecture and function of damaged/diseased lungs remain underexplored. Published data have revealed that alveolar progenitor type II cell (ATIIC)-derived signaling promotes re-epithelialization of injured alveoli, yet the underlying mechanism is unknown. Here we aim to define the role of ATIIC-derived exosome miRNA signaling in controlling ATIIC-specific proliferation or differentiation in response to injury.MethodsPluripotent stem cell-derived cultures, which contain early lung stem/progenitor populations that can subsequently differentiate into ATIICs, were used as a model for unbiased screening and identification of ATIIC phenotype-specific exosome miRNA signaling, and human induced pluripotent stem cell-derived ATIICs (hiPSC-ATIICs) were employed to examine the molecular basis of key exosome miRNA signaling in promoting ATIIC-specific proliferation. QRT-PCR was performed to examine expression pattern of ATIIC-derived key exosome miRNA in an alveolar injury model and in injured human lungs.ResultsWe show that human ATIIC line (A549)-derived exosome miR-371b-5p promotes ATIIC-specific proliferation, but not differentiation, in differentiating cultures of pluripotent stem cells. Using 3′UTR-driven luciferase reporters, we identified PTEN as a direct target of miR-371b-5p. Transfection of miR-371b-5p mimic into hiPSC-ATIICs leads to significantly decreased expression of endogenous PTEN, which stimulates phosphorylation of Akt and its downstream substrates, GSK3β and FOXOs, promoting cell proliferation. While not expressed in normal ATIIC phenotypes, the exosome miR-371b-5p expression is significantly induced after hiPSC-ATIICs or hATIICs (human primary ATIICs) are subjected to bleomycin-induced injury. To rule out that the ATIIC-derived exosome-miRNAs are merely a cell culture phenomenon, we transplanted hiPSC-ATIICs into bleomycin-challenged lungs of mice, and found that the transplanted hiPSC-ATIICs engraft and express exosome miR-371b-5p, along with additional survival of numerous mouse ATIICs in bleomycin-injured lungs. Consistent with these findings, significant levels of exosome miR-371b-5p were also detected in lavage samples of patients with acute pneumonia, but not in those from patients without pulmonary disorders.ConclusionsCollectively, our data strongly suggest that ATIIC-derived exosome miR-371b-5p may serve as a niche signaling to augment ATIIC survival/proliferation, promoting re-epithelialization of injured alveoli, and thus provide a promising novel target to develop treatment for currently incurable lung diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0586-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Exosome miR-371b-5p promotes proliferation of lung alveolar progenitor type II cells by using PTEN to orchestrate the PI3K/Akt signaling

et al. 2017

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“…81,84 Other successful examples based on this strategy included CD40L-modified lung cancer cells, CIITA-transfected CT26 cells and TNF-engineered J558 tumor cell. [85][86][87] Apart from genetic modification, external stimulus is added to drive tumor cell release of exosomes. We have extracted exosomes from a series of stress-induced tumor cells such as lymphoma cells, CEA-positive tumor cells, Lewis lung carcinoma and melanoma cells.…”

Section: Modified Tumor Cell-derived Exosomes (Texs)mentioning

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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“…Thus, the context in which they are presented is of high importance. Many different strategies, from using heat-shocked tumors cells [159,160] to having the cells express markers such as Hsp70 [161,162], CD40L [163], and Rab27a [164] have been proposed for improving immunogenicity. Instead of direct vaccination, tumor exosomes have been used as the antigenic material for pulsing dendritic cells to promote downstream immunity [165].…”

Section: Cell Membrane-based Nanostructuresmentioning

confidence: 99%

Cell membrane-derived nanomaterials for biomedical applications

et al. 2017

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The continued evolution of biomedical nanotechnology has enabled clinicians to better detect, prevent, manage, and treat human disease. In order to further push the limits of nanoparticle performance and functionality, there has recently been a paradigm shift towards biomimetic design strategies. By taking inspiration from nature, the goal is to create next-generation nanoparticle platforms that can more effectively navigate and interact with the incredibly complex biological systems that exist within the body. Of great interest are cellular membranes, which play essential roles in biointerfacing, self-identification, signal transduction, and compartmentalization. In this review, we explore the major ways in which researchers have directly leveraged cell membrane-derived biomaterials for the fabrication of novel nanotherapeutics and nanodiagnostics. Such emerging technologies have the potential to significantly advance the field of nanomedicine, helping to improve upon traditional modalities while also enabling novel applications.

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More efficient induction of antitumor T cell immunity by exosomes from CD40L gene-modified lung tumor cells

Cited by 63 publications

References 21 publications

Exosome miR-371b-5p promotes proliferation of lung alveolar progenitor type II cells by using PTEN to orchestrate the PI3K/Akt signaling

Exosome miR-371b-5p promotes proliferation of lung alveolar progenitor type II cells by using PTEN to orchestrate the PI3K/Akt signaling

The exosomes in tumor immunity

Cell membrane-derived nanomaterials for biomedical applications

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