bims-exocan 2023-08-27 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–08–27
eight papers selected by
Muhammad Rizwan, COMSATS University

Exosomal miRNA-mediated intercellular communications and immunomodulatory effects in tumor microenvironments.
Dendritic Cell-Derived Exosomes in Cancer Immunotherapy.
Unveiling the Yin-Yang Balance of M1 and M2 Macrophages in Hepatocellular Carcinoma: Role of Exosomes in Tumor Microenvironment and Immune Modulation.
Emerging role of exosome-derived non-coding RNAs in tumor-associated angiogenesis of tumor microenvironment.
Evaluation of Exosomal miRNA as Potential Biomarkers in Cervical Cancer.
Exosomal ACADM sensitizes gemcitabine-resistance through modulating fatty acid metabolism and ferroptosis in pancreatic cancer.
Sequential Targeting Hybrid Nanovesicles Composed of Chimeric Antigen Receptor T-Cell-Derived Exosomes and Liposomes for Enhanced Cancer Immunochemotherapy.
Biogenesis, Isolation, and Detection of Exosomes and Their Potential in Therapeutics and Diagnostics.

J Biomed Sci. 2023 Aug 21. 30(1): 69

Exosomal miRNA-mediated intercellular communications and immunomodulatory effects in tumor microenvironments.

Howida M Nail, Chien-Chih Chiu, Chung-Hang Leung, Mahmoud M M Ahmed, Hui-Min David Wang.

  Extracellular communication, in other words, crosstalk between cells, has a pivotal role in the survival of an organism. This communication occurs by different methods, one of which is extracellular vesicles. Exosomes, which are small lipid extracellular vesicles, have recently been discovered to have a role in signal transduction between cells inside the body. These vesicles contain important bioactive molecules including lipids, proteins, DNA, mRNA, and noncoding RNAs such as microRNAs (miRNAs). Exosomes are secreted by all cells including immune cells (macrophages, lymphocytes, granulocytes, dendritic cells, mast cells) and tumor cells. The tumor microenvironment (TME) represents a complex network that supports the growth of tumor cells. This microenvironment encompasses tumor cells themselves, the extracellular matrix, fibroblasts, endothelial cells, blood vessels, immune cells, and non-cellular components such as exosomes and cytokines. This review aims to provide insights into the latest discoveries concerning how the immune system communicates internally and with other cell types, with a specific focus on research involving exosomal miRNAs in macrophages, dendritic cells, B lymphocytes, and T lymphocytes. Additionally, we will explore the role of exosomal miRNA in the TME and the immunomodulatory effect.

Keywords:  Biogenesis; Cancer; Exosomes; Immune cells; Tumor microenvironment; miRNA

DOI:  https://doi.org/10.1186/s12929-023-00964-w
Pharmaceutics. 2023 Aug 01. pii: 2070. [Epub ahead of print]15(8):

Dendritic Cell-Derived Exosomes in Cancer Immunotherapy.

Shumin Luo, Jing Chen, Fang Xu, Huan Chen, Yiru Li, Weihua Li.

  Exosomes are nanoscale vesicles released by diverse types of cells for complex intercellular communication. Numerous studies have shown that exosomes can regulate the body's immune response to tumor cells and interfere with the tumor microenvironment (TME). In clinical trials on dendritic cell (DC)-based antitumor vaccines, no satisfactory results have been achieved. However, recent studies suggested that DC-derived exosomes (DEXs) may be superior to DC-based antitumor vaccines in avoiding tumor cell-mediated immunosuppression. DEXs contain multiple DC-derived surface markers that capture tumor-associated antigens (TAAs) and promote immune cell-dependent tumor rejection. These findings indicate the necessity of the further development and improvement of DEX-based cell-free vaccines to complement chemotherapy, radiotherapy, and other immunotherapies. In this review, we highlighted the recent progress of DEXs in cancer immunotherapy, particularly by concentrating on landmark studies and the biological characterization of DEXs, and we summarized their important role in the tumor immune microenvironment (TIME) and clinical application in targeted cancer immunotherapy. This review could enhance comprehension of advances in cancer immunotherapy and contribute to the elucidation of how DEXs regulate the TIME, thereby providing a reference for utilizing DEX-based vaccines in clinical practice.

Keywords:  cancer; dendritic cells; exosomes; immunotherapy

DOI:  https://doi.org/10.3390/pharmaceutics15082070
Cells. 2023 Aug 10. pii: 2036. [Epub ahead of print]12(16):

Unveiling the Yin-Yang Balance of M1 and M2 Macrophages in Hepatocellular Carcinoma: Role of Exosomes in Tumor Microenvironment and Immune Modulation.

Stavros P Papadakos, Nikolaos Machairas, Ioanna E Stergiou, Konstantinos Arvanitakis, Georgios Germanidis, Adam Enver Frampton, Stamatios Theocharis.

  Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate and limited treatment options. Recent research has brought attention to the significant importance of intercellular communication in the progression of HCC, wherein exosomes have been identified as critical agents facilitating cell-to-cell signaling. In this article, we investigate the impact of macrophages as both sources and targets of exosomes in HCC, shedding light on the intricate interplay between exosome-mediated communication and macrophage involvement in HCC pathogenesis. It investigates how exosomes derived from HCC cells and other cell types within the tumor microenvironment (TME) can influence macrophage behavior, polarization, and recruitment. Furthermore, the section explores the reciprocal interactions between macrophage-derived exosomes and HCC cells, stromal cells, and other immune cells, elucidating their role in tumor growth, angiogenesis, metastasis, and immune evasion. The findings presented here contribute to a better understanding of the role of macrophage-derived exosomes in HCC progression and offer new avenues for targeted interventions and improved patient outcomes.

Keywords:  exosomes; extracellular vesicles; hepatocellular carcinoma (HCC); immunotherapy; macrophages; tumor microenvironment (TME)

DOI:  https://doi.org/10.3390/cells12162036
Front Mol Biosci. 2023 ;10 1220193

Emerging role of exosome-derived non-coding RNAs in tumor-associated angiogenesis of tumor microenvironment.

Sai-Li Duan, Wei-Jie Fu, Ying-Ke Jiang, Lu-Shan Peng, Diabate Ousmane, Zhe-Jia Zhang, Jun-Pu Wang.

  The tumor microenvironment (TME) is an intricate ecosystem that is actively involved in various stages of cancer occurrence and development. Some characteristics of tumor biological behavior, such as proliferation, migration, invasion, inhibition of apoptosis, immune escape, angiogenesis, and metabolic reprogramming, are affected by TME. Studies have shown that non-coding RNAs, especially long-chain non-coding RNAs and microRNAs in cancer-derived exosomes, facilitate intercellular communication as a mechanism for regulating angiogenesis. They stimulate tumor growth, as well as angiogenesis, metastasis, and reprogramming of the TME. Exploring the relationship between exogenous non-coding RNAs and tumor-associated endothelial cells, as well as their role in angiogenesis, clinicians will gain new insights into treatment as a result.

Keywords:  cancer; endothelial cells; exosomes; exosomes-derived non-coding RNAs; lncRNA; miRNA; tumor microenvironment; tumorassociated angiogenesis

DOI:  https://doi.org/10.3389/fmolb.2023.1220193
Epigenomes. 2023 Aug 01. pii: 16. [Epub ahead of print]7(3):

Evaluation of Exosomal miRNA as Potential Biomarkers in Cervical Cancer.

Jéssika Aline do Nascimento Medeiros, Ayane Cristine Alves Sarmento, Emanuelly Bernardes-Oliveira, Ronnier de Oliveira, Maysa Eunice Grigorio Bezerra Lima, Ana Katherine Gonçalves, Deyse de Souza Dantas, Janaina Cristiana de Oliveira Crispim.

  Different studies show that small non-coding RNAs, such as microRNAs (miRNAs) obtained from exosomes, are considered potential biomarkers in several types of cancer, including cervical cancer (CC). Therefore, the present study seeks to present an overview of the role of circulating exosomal miRNAs with the potential to act as biomarkers for the diagnosis and prognosis of CC and to analyze the presence of these miRNAs according to the stage of CC. For this purpose, a review was developed, with articles consulted from the electronic databases MEDLINE/PubMed, Scopus, and Web of Science published between 2015 and 2021. Seven articles were included after a selection of studies according to the eligibility criteria. In addition to the methods used for sample analysis, detection, and isolation of miRNAs in each article, clinical data were also extracted from the patients studied, such as the stage of cancer. After analyzing the network of the seven miRNAs, they were associated with the immune system, CC progression and staging, and cisplatin resistance. With the belief that studies on miRNAs in cervical cancer would have major clinical implications, in this review, we have attempted to summarize the current situation and potential development prospects.

Keywords:  biomarkers; cervical cancer; exosomes; miRNAs

DOI:  https://doi.org/10.3390/epigenomes7030016
BMC Cancer. 2023 Aug 23. 23(1): 789

Exosomal ACADM sensitizes gemcitabine-resistance through modulating fatty acid metabolism and ferroptosis in pancreatic cancer.

Yuhan Yang, Haitao Gu, Kundong Zhang, Zengya Guo, Xiaofeng Wang, Qingyun Wei, Ling Weng, Xuan Han, Yan Lv, Meng Cao, Peng Cao, Chen Huang, Zhengjun Qiu.

  This study aimed to evaluate the potential of exosomes from cancer cells to predict chemoresistance in pancreatic cancer (PC) and explore the molecular mechanisms through RNA-sequencing and mass spectrometry. We sought to understand the connection between the exosomal Medium-chain acyl-CoA dehydrogenase (ACADM) level and the reaction to gemcitabine in vivo and in patients with PC. We employed loss-of-function, gain-of-function, metabolome mass spectrometry, and xenograft models to investigate the effect of exosomal ACADM in chemoresistance in PC. Our results showed that the molecules involved in lipid metabolism in exosomes vary between PC cells with different gemcitabine sensitivity. Exosomal ACADM (Exo-ACADM) was strongly correlated with gemcitabine sensitivity in vivo, which can be used as a predictor for postoperative gemcitabine chemosensitivity in pancreatic patients. Moreover, ACADM was found to regulate the gemcitabine response by affecting ferroptosis through Glutathione peroxidase 4 (GPX4) and mevalonate pathways. It was also observed that ACADM increased the consumption of unsaturated fatty acids and decreased intracellular lipid peroxides and reactive oxygen species (ROS) levels. In conclusion, this research suggests that Exo-ACADM may be a viable biomarker for predicting the responsiveness of patients to chemotherapy.

Keywords:  Biomarker; Exosomes; Ferroptosis; Gemcitabine; Lipid metabolism; Pancreatic cancer

DOI:  https://doi.org/10.1186/s12885-023-11239-w
ACS Nano. 2023 Aug 25.

Sequential Targeting Hybrid Nanovesicles Composed of Chimeric Antigen Receptor T-Cell-Derived Exosomes and Liposomes for Enhanced Cancer Immunochemotherapy.

Tianchuan Zhu, Zhenxing Chen, Guanmin Jiang, Xi Huang.

  Paclitaxel (PTX)-based chemotherapy remains the main approach to treating lung cancer but systemic toxicity limits its use. As chimeric antigen receptor-T (CAR-T) cell-derived exosomes contain tumor-targeted CARs and cytotoxic granules (granzyme B and perforin), they are considered potential delivery vehicles for PTX. However, the low drug-loading capacity and hepatotropic properties of exosomes are obstacles to their application to extrahepatic cancer. Here, a hybrid nanovesicle named Lip-CExo@PTX was designed for immunochemotherapy of lung cancer by fusing exosomes derived from bispecific CAR-T cells targeting both mesothelin (MSLN) and programmed death ligand-1 (PD-L1) with lung-targeted liposomes. Due to the lung-targeting ability of the liposomes, over 95% of intravenously administered Lip-CExo@PTX accumulated in lung tissue. In addition, with the help of the anti-MSLN single-chain variable fragment (scFv), the PTX and cytotoxic granules inside Lip-CExo@PTX were further delivered into MSLN-positive tumors. Notably, the anti-PD-L1 scFv on Lip-CExo@PTX blocked PD-L1 on the tumors to avoid T cell exhaustion and promoted PTX-induced immunogenic cell death. Furthermore, Lip-CExo@PTX prolonged the survival time of tumor-bearing mice in a CT-26 metastatic lung cancer model. Therefore, Lip-CExo@PTX may deliver PTX to tumor cells through sequential targeted delivery and enhance the antitumor effects, providing a promising strategy for immunochemotherapy of lung cancer.

Keywords:  CAR-T; Exosome; Hybrid nanovesicles; Immune checkpoint blockade; Immunochemotherapy; Immunogenic cell death; Liposome

DOI:  https://doi.org/10.1021/acsnano.3c03456
Biosensors (Basel). 2023 Aug 10. pii: 802. [Epub ahead of print]13(8):

Biogenesis, Isolation, and Detection of Exosomes and Their Potential in Therapeutics and Diagnostics.

Smrity Sonbhadra, Mehak, Lalit M Pandey.

  The increasing research and rapid developments in the field of exosomes provide insights into their role and significance in human health. Exosomes derived from various sources, such as mesenchymal stem cells, cardiac cells, and tumor cells, to name a few, can be potential therapeutic agents for the treatment of diseases and could also serve as biomarkers for the early detection of diseases. Cellular components of exosomes, several proteins, lipids, and miRNAs hold promise as novel biomarkers for the detection of various diseases. The structure of exosomes enables them as drug delivery vehicles. Since exosomes exhibit potential therapeutic applications, their efficient isolation from complex biological/clinical samples and precise real-time analysis becomes significant. With the advent of microfluidics, nano-biosensors are being designed to capture exosomes efficiently and rapidly. Herein, we have summarized the history, biogenesis, characteristics, functions, and applications of exosomes, along with the isolation, detection, and quantification techniques. The implications of surface modifications to enhance specificity have been outlined. The review also sheds light on the engineered nanoplatforms being developed for exosome detection and capture.

Keywords:  biomarkers; biosensors; diagnostic applications; exosomes; micro-RNA; therapeutic potential

DOI:  https://doi.org/10.3390/bios13080802