DNA analysis of low‐ and high‐density fractions defines heterogeneous subpopulations of small extracellular vesicles based on their DNA cargo and topology

Lázaro-Ibáñez, Elisa; Lässer, Cecilia; Shelke, Ganesh Vilas; Crescitelli, Rossella; Jang, Su Chul; Cvjetkovic, Aleksander; García-Rodríguez, A.; Lötvall, Jan

doi:10.1080/20013078.2019.1656993

Cited by 146 publications

(173 citation statements)

References 45 publications

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“…[10][11][12] Nevertheless, the proportion of ctDNA engulfed into extracellular vesicles actively released by tumour cells is still unclear and the effect of different therapy regimens on this active secretion mostly unknown. 13,14 Obviously, there is a huge need for more fundamental research on the kinetics of ctDNA in cancer patients.…”

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confidence: 99%

Clinical relevance of blood-based ctDNA analysis: mutation detection and beyond

et al. 2020

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Cell-free DNA (cfDNA) derived from tumours is present in the plasma of cancer patients. The majority of currently available studies on the use of this circulating tumour DNA (ctDNA) deal with the detection of mutations. The analysis of cfDNA is often discussed in the context of the noninvasive detection of mutations that lead to resistance mechanisms and therapeutic and disease monitoring in cancer patients. Indeed, substantial advances have been made in this area, with the development of methods that reach high sensitivity and can interrogate a large number of genes. Interestingly, however, cfDNA can also be used to analyse different features of DNA, such as methylation status, size fragment patterns, transcriptomics and viral load, which open new avenues for the analysis of liquid biopsy samples from cancer patients. This review will focus on the new perspectives and challenges of cfDNA analysis from mutation detection in patients with solid malignancies.

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confidence: 99%

Clinical relevance of blood-based ctDNA analysis: mutation detection and beyond

et al. 2020

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“…It has been demonstrated that exosomes can transfer specific proteins, nucleic acids, and lipids from donor cells to recipient cells, thereby influencing the phenotype of the recipient cells (Milane et al, 2015;Ruivo et al, 2017;Wan et al, 2018;Lazaro-Ibanez et al, 2019). Recent studies found that tumor-derived exosomes can transport PD-L1 from PD-L1-positive tumor cells to PD-L1-negative tumor cells (Yang et al, 2018).…”

Section: Exopd-l1 Interacts With Pd-1 On T Cells After Migration To Pmentioning

confidence: 99%

Exosomal PD-L1: New Insights Into Tumor Immune Escape Mechanisms and Therapeutic Strategies

Zhou

Guo

et al. 2020

Front. Cell Dev. Biol.

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As a classical immune checkpoint molecule, PD-L1 on the surface of tumor cells plays a pivotal role in tumor immunosuppression, primarily by inhibiting the antitumor activities of T cells by binding to its receptor PD-1. PD-1/PD-L1 inhibitors have demonstrated unprecedented promise in treating various human cancers with impressive efficacy. However, a significant portion of cancer patients remains less responsive. Therefore, a better understanding of PD-L1-mediated immune escape is imperative. PD-L1 can be expressed on the surface of tumor cells, but it is also found to exist in extracellular forms, such as on exosomes. Recent studies have revealed the importance of exosomal PD-L1 (ExoPD-L1). As an alternative to membrane-bound PD-L1, ExoPD-L1 produced by tumor cells also plays an important regulatory role in the antitumor immune response. We review the recent remarkable findings on the biological functions of ExoPD-L1, including the inhibition of lymphocyte activities, migration to PD-L1-negative tumor cells and immune cells, induction of both local and systemic immunosuppression, and promotion of tumor growth. We also discuss the potential implications of ExoPD-L1 as a predictor for disease progression and treatment response, sensitive methods for detection of circulating ExoPD-L1, and the novel therapeutic strategies combining the inhibition of exosome biogenesis with PD-L1 blockade in the clinic.

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“…A study characterized subpopulations within the EV population with different DNA and RNA content and topology. In addition, they identified two types of DNAs, internally protected and external surface-related DNA, that could be used as a basis for developing diagnostic methods [68,69].…”

Section: Extracellular Vesicles As Ideal Cancer Biomarkersmentioning

confidence: 99%

Liquid biopsy using extracellular vesicle–derived DNA in lung adenocarcinoma

Kim

Hur

Kim

et al. 2020

J Pathol Transl Med

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A growing trend in identifying biomarkers in diseases has brought on a dramatic rise in the number of tissue biopsies performed in the era of precision medicine. With advanced non-small cell lung cancer (NSCLC) patients often relying on small biopsies, the clinical need for an established liquid biopsy protocol has become an urgent necessity. Unlike gastrointestinal cancer, where tumor lesions in all locations can generally be visualized, lung cancers can only be approached by bronchoscopy, which limits visualization to central tumors. Even with the use of endobronchial ultrasound, peripheral lung cancers, such as adenocarcinoma before metastasis to the mediastinal lymph node, must rely on the invasive percutaneous needle biopsy (PCNB). Recent trends have shown a decrease in the incidence of central lung cancers, such as squamous cell carcinoma and small cell carcinoma, with a concomitant increase in the incidence adenocarcinoma, where testing to identify driver oncogenic mutations is essentially useful [1-3]. With the development of target therapy drugs, the clinical need for rebiopsy or even repeated biopsies is increasing in order to identify drug resistance mechanisms in the targeted tissues [4,5]. Lung cancer tumor lesions are often small in size or positioned in a way that makes them difficult to target. In the case of ground-glass nodules (GGNs), a biopsy is not possible until enough of a solid portion develops to obtain tumor tissue by PCNB. For these reasons, "tissue is the issue" is a challenge faced by many clinicians, especially by those treating lung cancers. Liquid biopsy using blood was introduced to over

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DNA analysis of low‐ and high‐density fractions defines heterogeneous subpopulations of small extracellular vesicles based on their DNA cargo and topology

Cited by 146 publications

References 45 publications

Clinical relevance of blood-based ctDNA analysis: mutation detection and beyond

Clinical relevance of blood-based ctDNA analysis: mutation detection and beyond

Exosomal PD-L1: New Insights Into Tumor Immune Escape Mechanisms and Therapeutic Strategies

Liquid biopsy using extracellular vesicle–derived DNA in lung adenocarcinoma

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