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Tumor-derived exosomes

Song Han, David H Gonzalo, Michael Feely, Carlos Rinaldi, Sayali Belsare, Haiyan Zhai, Krishan Kalra, Michael H Gerber, Christopher E Forsmark, Steven J Hughes
The biology of tumor-associated stroma (TAS) in pancreatic ductal adenocarcinoma (PDAC) is not well understood. The paradoxical observation that stroma-depletion strategies lead to progression of PDAC reinforced the need to critically evaluate the functional contribution of TAS in the initiation and progression of PDAC. PDAC and TAS cells are unique in their expression of specific miRNAs, and this specific miRNA expression pattern alters host to tumor microenvironment interactions. Using primary human pancreatic TAS cells and primary xenograft PDAC cells co-culture, we provide evidence of miRNA trafficking and exchanging between TAS and PDAC cells, in a two-way, cell-contact independent fashion, via extracellular vesicles (EVs) transportation...
January 19, 2018: Oncotarget
Margot Zöller
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells originally described to hamper immune responses in chronic infections. Meanwhile, they are known to be a major obstacle in cancer immunotherapy. On the other hand, MDSC can interfere with allogeneic transplant rejection and may dampen autoreactive T cell activity. Whether MDSC-Exosomes (Exo) can cope with the dangerous and potentially therapeutic activities of MDSC is not yet fully explored. After introducing MDSC and Exo, it will be discussed, whether a blockade of MDSC-Exo could foster the efficacy of immunotherapy in cancer and mitigate tumor progression supporting activities of MDSC...
2018: Frontiers in Immunology
Jianwei Gao, Xiangyu Qiu, Xinying Li, Hang Fan, Fang Zhang, Tangfeng Lv, Yong Song
Exosomes are membrane-bound, virus-size vesicles present in circulating blood. Tumor cells are avid producers of exosomes, which are thought to mimic molecular features of parent tumor cells. T-cell Immunoglobulin- and Mucin-domain-containing molecule 3 (Tim-3) is one of the next generation immune checkpoints and can be activated by its ligand Galectin-9, negatively regulating anti-tumor immune response. However, the characteristics of plasma exosomal Tim-3/Galectin-9 (Exo-T/G) in cancer remained unknown. Our study aimed to investigate the expression patterns and clinical value of plasma exosomal total protein (Exo-pro) and Exo-T/G in non-small cell lung caner (NSCLC)...
February 13, 2018: Biochemical and Biophysical Research Communications
Ivana Bratić Hench, Jürgen Hench, Markus Tolnay
Examination of tumor molecular characteristics by liquid biopsy is likely to greatly influence personalized cancer patient management. Analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and tumor-derived exosomes, all collectively referred to as "liquid biopsies," are not only a modality to monitor treatment efficacy, disease progression, and emerging therapy resistance mechanisms, but they also assess tumor heterogeneity and evolution in real time. We review the literature concerning the examination of ctDNA and CTC in a diagnostic setting, evaluating their prognostic, predictive, and monitoring capabilities...
2018: Frontiers in Medicine
Xiaoyue Jiang, Shenfei Zong, Chen Chen, Yizhi Zhang, Zhuyuan Wang, Yiping Cui
As a novel fluorescent nanomaterial, gold-carbon quantum dots (GCDs) possess high biocompatibility and can be easily synthesized by a microwave-assisted method. Owing to their small sizes and unique optical properties, GCDs can be applied to imaging of biological targets, such as cells, exosomes and other organelles. In this study, GCDs were used for fluorescence imaging of exosomes. Tumor-specific antibodies are attached to the GCDs, forming exosome specific nanoprobes. The nanoprobes can label exosomes via immuno-reactions and thus facilitate fluorescent imaging of exosomes...
February 13, 2018: Nanotechnology
Marie-Nicole Theodoraki, Thomas K Hoffmann, Theresa L Whiteside
Head and neck squamous cell carcinoma (HNSCC) is a highly immunosuppressive malignancy. Exosomes in HNSCC patients' plasma are enriched in inhibitory cargo and mediate immunosuppression. As these exosomes are products of various cells, the cellular origin of immunoregulatory proteins they carry is unknown. To test whether tumor- or T cell-derived exosomes in patient's plasma are immunosuppressive and impact on disease activity, we separated CD3(-) from CD3(+) exosomes by immunocapture using anti-CD3 Abs. The exosome protein cargo was evaluated for immunoregulatory proteins using on-bead flow cytometry...
February 12, 2018: Clinical and Experimental Immunology
Shisheng Chen, Mingfen Lv, Shan Fang, Wenxia Ye, Yu Gao, Yunsheng Xu
Dendritic cell (DC)-derived exosomes (Dexo) has been confirmed to be able to induce the specific anti-tumor immune response ex vivo and in vivo. Here, the aim of this study was to evaluate the application of the antigen-pulsed Dexo as a new vaccination platform in immunotherapy for cervical cancer. The immunogenic profile of the different Dexo was assessed by the cell proliferation, cytokines secretion and effector functions of CD8+ T cells and the splenocytes from Dexo-vaccinated mice. Furthermore, the anti-tumor immunity elicited by Dexo was further compared in cervical cancer-bearing mice...
February 7, 2018: International Journal of Biological Macromolecules
Minako Ikoma, Soren Gantt, Corey Casper, Yuko Ogata, Qing Zhang, Ryan Basom, Michael R Dyen, Timothy M Rose, Serge Barcy
Kaposi's sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). Both KSHV and HIV infections are endemic in Uganda, where KS is among the most common cancers in HIV-infected individuals. Recent studies examined the use of small RNAs as biomarkers of disease, including microRNAs (miRNAs), with viral and tumor-derived miRNAs being detected in exosomes from individuals with KSHV-associated malignancies. In the current study, the host and viral extracellular mature miRNA expression profiles were analyzed in blood of KS-negative individuals in Uganda, comparing those with or without KSHV detectable from the oropharynx...
2018: PloS One
Hongyu Liu, Ling Chen, Yaojun Peng, Songyan Yu, Jialin Liu, Liangliang Wu, Lijun Zhang, Qiyan Wu, Xin Chang, Xinguang Yu, Tianyi Liu
Exosomes are vesicles that can be secreted by many types of cell and released into the extracellular space. Studies have found that tumor derived exosomes (TEXs) can promote tumor growth and metastasis, as well as inhibit immune response through transferring their genetic information to the recipient cells. Given their functions in tumor progression, TEXs are considered as promising biomarkers for early detection of human malignancy. Dendritic cells (DCs), a type of antigen presenting cells, can induce tumor-specific T cell immune responses in carcinogenesis...
January 5, 2018: Oncotarget
Xiaochen Wang, Haiyuan Shen, Guangyan Zhangyuan, Ruyi Huang, Wenjie Zhang, Qifeng He, Kangpeng Jin, Han Zhuo, Zechuan Zhang, Jincheng Wang, Beicheng Sun, Xiaojie Lu
Increasing evidence shows that the anti-tumor functions of tumor-infiltrating T lymphocytes (TILs) were inhibited significantly, but the underlying mechanisms remain not fully understood. In this study, we found that 14-3-3ζ expression was up-regulated in hepatocellular carcinoma (HCC) cells and in TILs. TILs with 14-3-3ζ high-expression (14-3-3ζhigh) exhibited impaired activation (CD69), proliferation (Ki67) and anti-tumor functions compared to 14-3-3ζ low expression (14-3-3ζlow) TILs. Flow cytometry assay showed that compared with 14-3-3ζlow CD8+T cells, 14-3-3ζhigh ones exhibited higher frequency of exhausted phenotypes as measured by inhibitory receptors such as PD-1, TIM-3, LAG3, and CTLA-4...
February 7, 2018: Cell Death & Disease
Takanori Eguchi, Chiharu Sogawa, Yuka Okusha, Kenta Uchibe, Ryosuke Iinuma, Kisho Ono, Keisuke Nakano, Jun Murakami, Manabu Itoh, Kazuya Arai, Toshifumi Fujiwara, Yuri Namba, Yoshiki Murata, Kazumi Ohyama, Manami Shimomura, Hirohiko Okamura, Masaharu Takigawa, Tetsuya Nakatsura, Ken-Ichi Kozaki, Kuniaki Okamoto, Stuart K Calderwood
Ability to form cellular aggregations such as tumorspheres and spheroids have been used as a morphological marker of malignant cancer cells and in particular cancer stem cells (CSC). However, the common definition of the types of cellular aggregation formed by cancer cells has not been available. We examined morphologies of 67 cell lines cultured on three dimensional morphology enhancing NanoCulture Plates (NCP) and classified the types of cellular aggregates that form. Among the 67 cell lines, 49 cell lines formed spheres or spheroids, 8 cell lines formed grape-like aggregation (GLA), 8 cell lines formed other types of aggregation, and 3 cell lines formed monolayer sheets...
2018: PloS One
Shengbin Shi, Quan Rao, Chuangnian Zhang, Xiuyuan Zhang, Yibo Qin, Zuoxing Niu
Advanced hepatocellular carcinoma (HCC) has limited therapeutic options. Immunotherapy is a promising treatment, while sorafenib is a first-line drug-based treatment for advanced HCC. However, the efficacy of sorafenib and immunotherapy in combination, have not been clearly evaluated. Sorafenib treatment has been shown to promote immunosuppression by increasing hypoxia in orthotopic HCC models. Here, we found that sorafenib treatment in mice with orthotopic HCC increased the expression of inhibitor programmed death-ligand 1 (PD-L1) and T-regulatory cells in tumor tissues...
January 27, 2018: Translational Oncology
Shaohua Cui, Zhuoan Cheng, Wenxin Qin, Liyan Jiang
In lung cancer and other malignancies, the so-called "liquid biopsy" is quickly moving into clinical practice. Its full potential has not yet been fully identified, but the "liquid biopsy" is no longer a promise but has become a reality that allows for better treatment selection and monitoring of lung cancer. This emerging field has significant potential to make up for the limitations of the traditional tissue-derived biomaterials. Exosomes are spherical nano-sized vesicles with a diameter of 40-100 nm and a density of 1...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Tae Sup Lee, Young Kim, Weiqi Zhang, In Ho Song, Ching-Hsuan Tung
BACKGROUND: Exosomes are nano-sized vesicles derived from the fusion of multivesicular bodies with the surrounding plasma membrane. Exosomes have various diagnostic and therapeutic potentials in cancer and other diseases, thus tracking exosomes is an important issue. METHODS: Here, we report a facile exosome labeling strategy using a natural metabolic incorporation of an azido-sugar into the glycan, and a strain-promoted azide-alkyne click reaction. In culture, tetra-acetylated N-azidoacetyl-D-mannosamine (Ac4ManNAz) was spontaneously incorporated into glycans within the cells and later redistributed onto their exosomes...
February 2, 2018: Biochimica et Biophysica Acta
Yawen Li, Yuan Liu, Fangming Xiu, Jianing Wang, Hua Cong, Shenyi He, Yongyu Shi, Xiaoyan Wang, Xun Li, Huaiyu Zhou
Introduction: Exosomes are nanograde membrane-bound vesicles secreted from most cell types through the fusion of multivesicular bodies with plasma membranes. Some of these exosomes are well defined, and are known to have immunomodulatory properties as well as play critical roles in intercellular communications. In this study, we characterized the exosomes derived from Toxoplasma gondii and their functions in aspect of immune responses. Methods: T. gondii exosomes were isolated and identified using electron microscopy, nanoparticle tracking analysis, and Western blotting...
2018: International Journal of Nanomedicine
Cassidy L Bland, Christina N Byrne-Hoffman, Audry Fernandez, Stephanie L Rellick, Wentao Deng, David J Klinke
While recent clinical studies demonstrate the promise of cancer immunotherapy, a barrier for broadening the clinical benefit is identifying how tumors locally suppress cytotoxic immunity. As an emerging mode of intercellular communication, exosomes secreted by malignant cells can deliver a complex payload of coding and non-coding RNA to cells within the tumor microenvironment. Here, we quantified the RNA pay-load within tumor-derived exosomes and the resulting dynamic transcriptomic response to cytotoxic T cells upon exosome delivery to better understand how tumor-derived exosomes can alter immune cell function...
February 5, 2018: FEBS Journal
Amogha Tadimety, Andrew Closson, Cathy Li, Song Yi, Ting Shen, John X J Zhang
Liquid biopsy, as a minimally invasive method of gleaning insight into the dynamics of diseases through a patient fluid sample, has been growing in popularity for cancer diagnosis, prognosis, and monitoring. While many technologies have been developed and validated in research laboratories, there has also been a push to expand these technologies into other clinical settings and as point of care devices. In this article, we discuss and evaluate microchip-based technologies for circulating tumor cell (CTC), exosome, and circulating tumor nucleic acid (ctNA) capture, detection, and analysis...
February 1, 2018: Critical Reviews in Clinical Laboratory Sciences
K P O'Brien, S Khan, K E Gilligan, H Zafar, P Lalor, C Glynn, C O'Flatharta, H Ingoldsby, P Dockery, A De Bhulbh, J R Schweber, K St John, M Leahy, J M Murphy, W M Gallagher, T O'Brien, M J Kerin, R M Dwyer
Adult Mesenchymal Stem Cells (MSCs) have a well-established tumor-homing capacity, highlighting potential as tumor-targeted delivery vehicles. MSCs secrete extracellular vesicle (EV)-encapsulated microRNAs, which play a role in intercellular communication. The aim of this study was to characterize a potential tumor suppressor microRNA, miR-379, and engineer MSCs to secrete EVs enriched with miR-379 for in vivo therapy of breast cancer. miR-379 expression was significantly reduced in lymph node metastases compared to primary tumor tissue from the same patients...
January 25, 2018: Oncogene
Liang Gao, Lin Wang, Tong Dai, Ke Jin, Zhengkui Zhang, Shuai Wang, Feng Xie, Pengfei Fang, Bing Yang, Huizhe Huang, Hans van Dam, Fangfang Zhou, Long Zhang
Malignancies can compromise innate immunity, but the mechanisms of this are largely unknown. Here we found that, via tumor-derived exosomes (TEXs), cancers were able to transfer activated epidermal growth factor receptor (EGFR) to host macrophages and thereby suppress innate antiviral immunity. Screening of the human kinome identified the kinase MEKK2 in macrophages as an effector of TEX-delivered EGFR that negatively regulated the antiviral immune response. In the context of experimental tumor implantation, MEKK2-deficient mice were more resistant to viral infection than were wild-type mice...
January 22, 2018: Nature Immunology
Riko Kitazawa, Ryuma Haraguchi, Mana Fukushima, Sohei Kitazawa
Hard tissue homeostasis is regulated by the balance between bone formation by osteoblasts and bone resorption by osteoclasts. This physiologic process allows adaptation to mechanical loading and calcium homeostasis. Under pathologic conditions, however, this process is ill-balanced resulting in either over-resorption or over-formation of hard tissue. Local over-resorption by osteoclasts is typically observed in osteolytic metastases of malignancies, autoimmune arthritis, and giant cell tumor of bone (GCTB)...
January 22, 2018: Histochemistry and Cell Biology
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