scholarly journals Extracellular Vesicles: New Players in Lymphomas

2018 ◽  
Vol 20 (1) ◽  
pp. 41 ◽  
Author(s):  
Victor Navarro-Tableros ◽  
Yonathan Gomez ◽  
Giovanni Camussi ◽  
Maria Felice Brizzi
Keyword(s):  
Disease Progression ◽  
Extracellular Vesicles ◽  
Immune Escape ◽  
Predictive Biomarkers ◽  
Response To Treatment ◽  
Cell Of Origin ◽  
Invasive Treatment ◽  
Liquid Biopsies ◽  
Tumor Immune Escape ◽  
Clinical Tools

Lymphomas are heterogeneous diseases, and the term includes a number of histological subtypes that are characterized by different clinical behavior and molecular phenotypes. Valuable information on the presence of lymphoma cell-derived extracellular vesicles (LCEVs) in the bloodstream of patients suffering from this hematological cancer has recently been provided. In particular, it has been reported that the number and phenotype of LCEVs can both change as the disease progresses, as well as after treatment. Moreover, the role that LCEVs play in driving tumor immune escape has been reported. This makes LCEVs potential novel clinical tools for diagnosis, disease progression, and chemoresistance. LCEVs express surface markers and convey specific molecules in accordance with their cell of origin, which can be used as targets and thus lead to the development of specific therapeutics. This may be particularly relevant since circulating LCEVs are known to save lymphoma cells from anti-cluster of differentiation (CD)20-induced complement-dependent cytotoxicity. Therefore, effort should be directed toward investigating the feasibility of using LCEVs as predictive biomarkers of disease progression and/or response to treatment that can be translated to clinical use. The use of liquid biopsies in combination with serum EV quantification and cargo analysis have been also considered as potential approaches that can be pursued in the future. Upcoming research will also focus on the identification of specific molecular targets in order to generate vaccines and/or antibodies against LCEVs. Finally, the removal of circulating LCEVs has been proposed as a simple and non-invasive treatment approach. We herein provide an overview of the role of LCEVs in lymphoma diagnosis, immune tolerance, and drug resistance. In addition, alternative protocols that utilize LCEVs as therapeutic targets are discussed.

scholarly journals Molecular Profile Study of Extracellular Vesicles for the Identification of Useful Small “Hit” in Cancer Diagnosis

2021 ◽  
Vol 11 (22) ◽  
pp. 10787
Author(s):  
Giusi Alberti ◽  
Christian M. Sánchez-López ◽  
Alexia Andres ◽  
Radha Santonocito ◽  
Claudia Campanella ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Biological Fluids ◽  
Cell Communication ◽  
Response To Treatment ◽  
Molecular Profile ◽  
Cell Of Origin ◽  
Liquid Biopsies ◽  
Precision Therapy

Tumor-secreted extracellular vesicles (EVs) are the main mediators of cell-cell communication, permitting cells to exchange proteins, lipids, and metabolites in varying physiological and pathological conditions. They contain signature tumor-derived molecules that reflect the intracellular status of their cell of origin. Recent studies have shown that tumor cell-derived EVs can aid in cancer metastasis through the modulation of the tumor microenvironment, suppression of the immune system, pre-metastatic niche formation, and subsequent metastasis. EVs can easily be isolated from a variety of biological fluids, and their content makes them useful biomarkers for the diagnosis, prognosis, monitorization of cancer progression, and response to treatment. This review aims to explore the biomarkers of cancer cell-derived EVs obtained from liquid biopsies, in order to understand cancer progression and metastatic evolution for early diagnosis and precision therapy.

scholarly journals Molecular and Circulating Biomarkers of Brain Tumors

2021 ◽  
Vol 22 (13) ◽  
pp. 7039
Author(s):  
Wojciech Jelski ◽  
Barbara Mroczko
Keyword(s):  
Brain Tumors ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Extracellular Vesicles ◽  
Dna Methyltransferase ◽  
Growth Factor Receptor ◽  
Response To Treatment ◽  
Liquid Biopsies ◽  
Methylguanine Dna Methyltransferase ◽  
The Central Nervous System

Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain tumors release molecular information into the circulation. Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a substitute for tumor tissue. Tumor-derived biomarkers include nucleic acids, proteins, and tumor-derived extracellular vesicles that accumulate in blood or cerebrospinal fluid. In recent years, circulating tumor cells have also been identified in the blood of glioblastoma patients. In this review of the literature, the authors highlight the significance, regulation, and prevalence of molecular biomarkers such as O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor, and isocitrate dehydrogenase. Herein, we critically review the available literature on plasma circulating tumor cells (CTCs), cell-free tumors (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), and circulating extracellular vesicles (EVs) for the diagnosis and monitoring of brain tumor. Currently available markers have significant limitations.While much research has been conductedon these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature.

scholarly journals Recent Advances in the Discovery of Biomarkers for Canine Osteosarcoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Anita K. Luu ◽  
Geoffrey A. Wood ◽  
Alicia M. Viloria-Petit
Keyword(s):  
Clinical Practice ◽  
Standard Treatment ◽  
Predictive Biomarkers ◽  
Response To Treatment ◽  
Liquid Biopsies ◽  
Future Directions ◽  
Diagnostic Biomarkers ◽  
Canine Osteosarcoma ◽  
The Past ◽  
Biomarker Research

Canine osteosarcoma (OSA) is an aggressive malignancy that frequently metastasizes to the lung and bone. Not only has there been essentially no improvement in therapeutic outcome over the past 3 decades, but there is also a lack of reliable biomarkers in clinical practice. This makes it difficult to discriminate which patients will most benefit from the standard treatment of amputation and adjuvant chemotherapy. The development of reliable diagnostic biomarkers could aid in the clinical diagnosis of primary OSA and metastasis; while prognostic, and predictive biomarkers could allow clinicians to stratify patients to predict response to treatment and outcome. This review summarizes biomarkers that have been explored in canine OSA to date. The focus is on molecular biomarkers identified in tumor samples as well as emerging biomarkers that have been identified in blood-based (liquid) biopsies, including circulating tumor cells, microRNAs, and extracellular vesicles. Lastly, we propose future directions in biomarker research to ensure they can be incorporated into a clinical setting.

scholarly journals High IKZF2 Expression in Malignant T cells Promotes Disease Progression in Cutaneous T cell Lymphoma

2021 ◽  
Author(s):  
Bufang Xu ◽  
Fengjie Liu ◽  
Yumei Gao ◽  
Jingru Sun ◽  
Yingyi Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Progression ◽  
Immune Escape ◽  
Cell Lymphoma ◽  
Malignant Cell ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Tumor Immune Escape ◽  
Malignant T Cells

Cutaneous T cell lymphoma is a generally indolent disease derived from skin-homing mature T cells. However, in advanced stages, CTCL may manifest as aggressive clinical behavior and lead to a poor prognosis. The mechanism of disease progression in CTCL remains unknown. Here, with a large clinical cohort, we identified that IKZF2, an essential transcription factor during T cell development and differentiation, showed stage-dependent overexpression in the malignant T cells in MF lesions. IKZF2 is specifically over-expressed in advanced-stage MF lesions, correlates with poor patient prognosis. Mechanistically, IKZF2 overexpression promotes CTCL progression via inhibiting malignant cell apoptosis and may contribute to tumor immune escape by downregulating MHC-II molecules and up-regulating the production of anti-inflammatory cytokine IL-10 by malignant T cells. These results demonstrate the important role of IKZF2 in high-risk CTCL and pave the way for future targeted therapy.

scholarly journals Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

2020 ◽  
Vol 21 (7) ◽  
pp. 2286 ◽  
Author(s):  
Stefania Raimondo ◽  
Marzia Pucci ◽  
Riccardo Alessandro ◽  
Simona Fontana
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Immune Escape ◽  
Immune Checkpoints ◽  
Cancer Therapies ◽  
Biological Functions ◽  
Hallmarks Of Cancer ◽  
Tumor Immune Escape

The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in regulating immune checkpoints, focusing on the PD-L1/PD-1 axis.

scholarly journals Exosomes and Extracellular Vesicles in Myeloid Neoplasia: The Multiple and Complex Roles Played by These “Magic Bullets”

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 105
Author(s):  
Simona Bernardi ◽  
Mirko Farina
Keyword(s):  
Extracellular Vesicles ◽  
New Technologies ◽  
Cell Communication ◽  
Response To Treatment ◽  
Liquid Biopsies ◽  
Disease Biomarkers ◽  
Mediate Cell ◽  
Therapeutic Tools ◽  
Myeloid Neoplasia ◽  
Multicellular Organisms

Extracellular vesicles (exosomes, in particular) are essential in multicellular organisms because they mediate cell-to-cell communication via the transfer of secreted molecules. They are able to shuttle different cargo, from nucleic acids to proteins. The role of exosomes has been widely investigated in solid tumors, which gave us surprising results about their potential involvement in pathogenesis and created an opening for liquid biopsies. Less is known about exosomes in oncohematology, particularly concerning the malignancies deriving from myeloid lineage. In this review, we aim to present an overview of immunomodulation and the microenvironment alteration mediated by exosomes released by malicious myeloid cells. Afterwards, we review the studies reporting the use of exosomes as disease biomarkers and their influence in response to treatment, together with the recent experiences that have focused on the use of exosomes as therapeutic tools. The further development of new technologies and the increased knowledge of biological (exosomes) and clinical (myeloid neoplasia) aspects are expected to change the future approaches to these malignancies.

scholarly journals Resistance Mechanisms to Combined CDK4/6 Inhibitors and Endocrine Therapy in ER+/HER2− Advanced Breast Cancer: Biomarkers and Potential Novel Treatment Strategies

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5397
Author(s):  
Abeer J. Al-Qasem ◽  
Carla L. Alves ◽  
Henrik J. Ditzel
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Disease Progression ◽  
Endocrine Therapy ◽  
Combined Therapy ◽  
Predictive Biomarkers ◽  
Resistance Mechanisms ◽  
Genetic Alterations ◽  
Advanced Breast ◽  
Liquid Biopsies

The introduction of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) has revolutionized the treatment landscape for patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC) and has become the new standard treatment. However, resistance to this combined therapy inevitably develops and represents a major clinical challenge in the management of ER+ ABC. Currently, elucidation of the resistance mechanisms, identification of predictive biomarkers, and development of novel effective combined targeted treatments to overcome the resistance are active areas of research. Given the heterogeneity of the resistance mechanisms towards combined CDK4/6i and ET, identification of a single universal predictive biomarker of resistance is unlikely. Novel approaches are being explored, including examination of multiple genetic alterations in circulating cell-free tumor DNA in liquid biopsies from ABC patients with disease progression on combined CDK4/6i and ET treatment. Here, we review the molecular basis of the main known resistance mechanisms towards combined CDK4/6i and ET and associated potential biomarkers. As inhibiting key molecules in the pathways driving resistance may play an important role in the selection of therapeutic strategies for patients who experience disease progression on combined CDK4/6i and ET, we also review preclinical and early phase clinical data on novel combination therapies for these patients.

scholarly journals Extracellular Vesicles in Hematological Malignancies: From Biomarkers to Therapeutic Tools

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1065
Author(s):  
Jihane Khalife ◽  
James F. Sanchez ◽  
Flavia Pichiorri
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Hematological Malignancies ◽  
Immune Surveillance ◽  
Therapeutic Targets ◽  
Molecular Signature ◽  
Response To Treatment ◽  
Clinical Tool ◽  
Liquid Biopsies ◽  
Disease Stratification

Small extracellular vesicles (EVs) are a heterogenous group of lipid particles released by all cell types in physiological and pathological states. In hematological malignancies, tumor-derived EVs are critical players in mediating intercellular communications through the transfer of genetic materials and proteins between neoplastic cells themselves and to several components of the bone marrow microenvironment, rendering the latter a “stronger” niche supporting cancer cell proliferation, drug resistance, and escape from immune surveillance. In this context, the molecular cargoes of tumor-derived EVs reflect the nature and status of the cells of origin, making them specific therapeutic targets. Another important characteristic of EVs in hematological malignancies is their use as a potential “liquid biopsy” because of their high abundance in biofluids and their ability to protect their molecular cargoes from nuclease and protease degradation. Liquid biopsies are non-invasive blood tests that provide a molecular profiling clinical tool as an alternative method of disease stratification, especially in cancer patients where solid biopsies have limited accessibility. They offer accurate diagnoses and identify specific biomarkers for monitoring of disease progression and response to treatment. In this review, we will focus on the role of EVs in the most prevalent hematological malignancies, particularly on their prospective use as biomarkers in the context of liquid biopsies, as well as their molecular signature that identifies them as specific therapeutic targets for inhibiting cancer progression. We will also highlight their roles in modulating the immune response by acting as both immunosuppressors and activators of anti-tumor immunity.

scholarly journals Extracellular Vesicles in the Tumour Microenvironment: Eclectic Supervisors

2020 ◽  
Vol 21 (18) ◽  
pp. 6768
Author(s):  
Claudia Cavallari ◽  
Giovanni Camussi ◽  
Maria Felice Brizzi
Keyword(s):  
Extracellular Vesicles ◽  
Immune Escape ◽  
Current Knowledge ◽  
Cell Communication ◽  
Tumour Microenvironment ◽  
Cancer Cell Proliferation ◽  
Cell Of Origin ◽  
Remote Sites ◽  
Survival And Growth ◽  
Cellular Components

The tumour microenvironment (TME) plays a crucial role in the regulation of cell survival and growth by providing inhibitory or stimulatory signals. Extracellular vesicles (EV) represent one of the most relevant cell-to-cell communication mechanism among cells within the TME. Moreover, EV contribute to the crosstalk among cancerous, immune, endothelial, and stromal cells to establish TME diversity. EV contain proteins, mRNAs and miRNAs, which can be locally delivered in the TME and/or transferred to remote sites to dictate tumour behaviour. EV in the TME impact on cancer cell proliferation, invasion, metastasis, immune-escape, pre-metastatic niche formation and the stimulation of angiogenesis. Moreover, EV can boost or inhibit tumours depending on the TME conditions and their cell of origin. Therefore, to move towards the identification of new targets and the development of a novel generation of EV-based targeting approaches to gain insight into EV mechanism of action in the TME would be of particular relevance. The aim here is to provide an overview of the current knowledge of EV released from different TME cellular components and their role in driving TME diversity. Moreover, recent proposed engineering approaches to targeting cells in the TME via EV are discussed.

scholarly journals Role of Extracellular Vesicles in Hematological Malignancies

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Stefania Raimondo ◽  
Chiara Corrado ◽  
Lavinia Raimondi ◽  
Giacomo De Leo ◽  
Riccardo Alessandro
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Hematological Malignancies ◽  
Predictive Biomarkers ◽  
Cell Types ◽  
Target Cells ◽  
Specific Cell ◽  
Cell Of Origin ◽  
Cell Functions

In recent years the role of tumor microenvironment in the progression of hematological malignancies has been widely recognized. Recent studies have focused on how cancer cells communicate within the microenvironment. Among several factors (cytokines, growth factors, and ECM molecules), a key role has been attributed to extracellular vesicles (EV), released from different cell types. EV (microvesicles and exosomes) may affect stroma remodeling, host cell functions, and tumor angiogenesis by inducing gene expression modulation in target cells, thus promoting cancer progression and metastasis. Microvesicles and exosomes can be recovered from the blood and other body fluids of cancer patients and contain and deliver genetic and proteomic contents that reflect the cell of origin, thus constituting a source of new predictive biomarkers involved in cancer development and serving as possible targets for therapies. Moreover, due to their specific cell-tropism and bioavailability, EV can be considered natural vehicles suitable for drug delivery. Here we will discuss the recent advances in the field of EV as actors in hematological cancer progression, pointing out the role of these vesicles in the tumor-host interplay and in their use as biomarkers for hematological malignancies.

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