scholarly journals EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3019
Author(s):  
Artur Słomka ◽  
Tudor Mocan ◽  
Bingduo Wang ◽  
Iuliana Nenu ◽  
Sabine Urban ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Tumour Progression ◽  
Cell Communication ◽  
Tumour Microenvironment ◽  
Host Immune System ◽  
Mediated Communication ◽  
Cell Content ◽  
Cytokines And Chemokines ◽  
Liver Cancers ◽  
Cancer Types

For more than a decade, extracellular vesicles (EVs) have been in focus of science. Once thought to be an efficient way to eliminate undesirable cell content, EVs are now well-accepted as being an important alternative to cytokines and chemokines in cell-to-cell communication route. With their cargos, mainly consisting of functional proteins, lipids and nucleic acids, they can activate signalling cascades and thus change the phenotype of recipient cells at local and systemic levels. Their substantial role as modulators of various physiological and pathological processes is acknowledged. Importantly, more and more evidence arises that EVs play a pivotal role in many stages of carcinogenesis. Via EV-mediated communication, tumour cells can manipulate cells from host immune system or from the tumour microenvironment, and, ultimately, they promote tumour progression and modulate host immunity towards tumour’s favour. Additionally, the role of EVs in modulating resistance to pharmacological and radiological therapy of many cancer types has become evident lately. Our understanding of EV biology and their role in cancer promotion and drug resistance has evolved considerably in recent years. In this review, we specifically discuss the current knowledge on the association between EVs and gastrointestinal (GI) and liver cancers, including their potential for diagnosis and treatment.

scholarly journals The role of the tumour microenvironment in immunotherapy

2017 ◽  
Vol 24 (12) ◽  
pp. T283-T295 ◽  
Author(s):  
Stephan Gasser ◽  
Lina H K Lim ◽  
Florence S G Cheung
Keyword(s):  
Current Knowledge ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Tumour Immunity ◽  
Recent Success ◽  
Cytokines And Chemokines ◽  
Solid Malignancies ◽  
Variable Success ◽  
Molecular Patterns

Recent success in immunomodulating strategies in lung cancer and melanoma has prompted much enthusiasm in their potential to treat other advanced solid malignancies. However, their applications have shown variable success and are even ineffective against some tumours. The efficiency of immunotherapies relies on an immunogenic tumour microenvironment. The current field of cancer immunology has focused on understanding the interaction of cancer and host immune cells to break the state of immune tolerance and explain how molecular patterns of cytokines and chemokines affect tumour progression. Here, we review our current knowledge of how inherent properties of tumours and their different tumour microenvironments affect therapeutic outcome. We also discuss insights into recent multimodal therapeutic approaches that target tumour immune evasion and suppression to restore anti-tumour immunity.

scholarly journals Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy

2020 ◽  
Vol 9 (9) ◽  
pp. 2967
Author(s):  
Anne M. Macpherson ◽  
Simon C. Barry ◽  
Carmela Ricciardelli ◽  
Martin K. Oehler
Keyword(s):  
Ovarian Cancer ◽  
Immune System ◽  
Epithelial Ovarian Cancer ◽  
Current Knowledge ◽  
Tumour Microenvironment ◽  
Tumour Immunology ◽  
The Us ◽  
Cancer Types ◽  
Cancer Immunotherapeutic ◽  
Cancer Immunotherapies

Recent advances in the understanding of immune function and the interactions with tumour cells have led to the development of various cancer immunotherapies and strategies for specific cancer types. However, despite some stunning successes with some malignancies such as melanomas and lung cancer, most patients receive little or no benefit from immunotherapy, which has been attributed to the tumour microenvironment and immune evasion. Although the US Food and Drug Administration have approved immunotherapies for some cancers, to date, only the anti-angiogenic antibody bevacizumab is approved for the treatment of epithelial ovarian cancer. Immunotherapeutic strategies for ovarian cancer are still under development and being tested in numerous clinical trials. A detailed understanding of the interactions between cancer and the immune system is vital for optimisation of immunotherapies either alone or when combined with chemotherapy and other therapies. This article, in two main parts, provides an overview of: (1) components of the normal immune system and current knowledge regarding tumour immunology, biology and their interactions; (2) strategies, and targets, together with challenges and potential innovative approaches for cancer immunotherapy, with attention given to epithelial ovarian cancer.

scholarly journals Bacterial extracellular vesicles as cell-cell communication mediators

2020 ◽  
Vol 74 ◽  
pp. 572-588
Author(s):  
Anna Chudzik ◽  
Mariola Paściak
Keyword(s):  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Cell Communication ◽  
Drug Carriers ◽  
Host Cells ◽  
Ecological Niches ◽  
Signal Molecules ◽  
Host Immune System ◽  
Protective Function ◽  
Cell Cell

Extracellular vesicles constitute a heterogeneous group of nanoparticles, released by both prokaryotic and eukaryotic cells, which perform various biological functions and participate in cell-cell communication. Bacterial extracellular vesicles are made of lipids, proteins and nucleic acids. There are a number of hypotheses for the formation of extracellular vesicles, but the mechanisms of biogenesis of these structures remain unclear. Hardly soluble metabolites or signaling molecules, DNA and RNA are vesicles cargo. Extracellular vesicles have a protective function, they can eliminate other bacterial cells and participate in horizontal gene transfer. The enzymes contained inside the vesicles facilitate the acquisition of nutrients and help colonize various ecological niches. Signal molecules carried in the vesicles enable biofilm formation. In the secreted extracellular vesicles pathogenic microorganisms carry virulence factors, including toxins, into the host cells. Via vesicles, bacteria can also modulate the host immune system. Bacterial extracellular vesicles are promising vaccine candidates and can be used as drug carriers. The review discusses the current knowledge concerning biogenesis, composition, preparation methods, physiological functions and potential applications of extracellular vesicles secreted by prokaryotic cells.

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 3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4610
Author(s):  
Teresa Franchi-Mendes ◽  
Rodrigo Eduardo ◽  
Giacomo Domenici ◽  
Catarina Brito
Keyword(s):  
Tumour Progression ◽  
Critical Role ◽  
Cell Communication ◽  
Malignant Cell ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Precise Control ◽  
Cancer Models

The tumour microenvironment plays a critical role in tumour progression and drug resistance processes. Non-malignant cell players, such as fibroblasts, endothelial cells, immune cells and others, interact with each other and with the tumour cells, shaping the disease. Though the role of each cell type and cell communication mechanisms have been progressively studied, the complexity of this cellular network and its role in disease mechanism and therapeutic response are still being unveiled. Animal models have been mainly used, as they can represent systemic interactions and conditions, though they face recognized limitations in translational potential due to interspecies differences. In vitro 3D cancer models can surpass these limitations, by incorporating human cells, including patient-derived ones, and allowing a range of experimental designs with precise control of each tumour microenvironment element. We summarize the role of each tumour microenvironment component and review studies proposing 3D co-culture strategies of tumour cells and non-malignant cell components. Moreover, we discuss the potential of these modelling approaches to uncover potential therapeutic targets in the tumour microenvironment and assess therapeutic efficacy, current bottlenecks and perspectives.

scholarly journals Transcriptional census of epithelial-mesenchymal plasticity in cancer

2021 ◽  
Author(s):  
David P. Cook ◽  
Barbara C. Vanderhyden
Keyword(s):  
Immune Cell ◽  
Tumour Progression ◽  
Expression Patterns ◽  
Therapy Resistance ◽  
Tumour Microenvironment ◽  
Regulatory Mechanisms ◽  
Molecular Features ◽  
Limited Scale ◽  
Cancer Types ◽  
High Degree

ABSTRACTEpithelial-mesenchymal plasticity (EMP) contributes to tumour progression, promoting therapy resistance and immune cell evasion. Definitive molecular features of this plasticity have largely remained elusive due to the limited scale of most studies. Leveraging scRNA-seq data from 160 tumours spanning 8 different cancer types, we identify expression patterns associated with intratumoural EMP. Integrative analysis of these programs confirmed a high degree of diversity among tumours. These diverse programs are associated with combinations of various common regulatory mechanisms initiated from cues within the tumour microenvironment. We highlight that inferring regulatory features can inform effective therapeutics to restrict EMP.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia

2020 ◽  
Author(s):  
Guanghui Xu ◽  
Yuhao Wang ◽  
Hushan Zhang ◽  
Xueke She ◽  
Jianjun Yang
Keyword(s):  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
The Body ◽  
Low Grade ◽  
Ablative Therapies ◽  
Cancer Types ◽  
New Treatment ◽  
Well Differentiated

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

scholarly journals Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor, O-GlcNAcylation, Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types—Tumour Microenvironment and Metabolism

2020 ◽  
Vol 22 (1) ◽  
pp. 141
Author(s):  
George Anderson
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Glycogen Synthase ◽  
Tumour Progression ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Future Research ◽  
Acetyl Coa ◽  
Dynamic Interactions ◽  
Aryl Hydrocarbon ◽  
Metabolic Interactions

This article reviews the dynamic interactions of the tumour microenvironment, highlighting the roles of acetyl-CoA and melatonergic pathway regulation in determining the interactions between oxidative phosphorylation (OXPHOS) and glycolysis across the array of cells forming the tumour microenvironment. Many of the factors associated with tumour progression and immune resistance, such as yin yang (YY)1 and glycogen synthase kinase (GSK)3β, regulate acetyl-CoA and the melatonergic pathway, thereby having significant impacts on the dynamic interactions of the different types of cells present in the tumour microenvironment. The association of the aryl hydrocarbon receptor (AhR) with immune suppression in the tumour microenvironment may be mediated by the AhR-induced cytochrome P450 (CYP)1b1-driven ‘backward’ conversion of melatonin to its immediate precursor N-acetylserotonin (NAS). NAS within tumours and released from tumour microenvironment cells activates the brain-derived neurotrophic factor (BDNF) receptor, TrkB, thereby increasing the survival and proliferation of cancer stem-like cells. Acetyl-CoA is a crucial co-substrate for initiation of the melatonergic pathway, as well as co-ordinating the interactions of OXPHOS and glycolysis in all cells of the tumour microenvironment. This provides a model of the tumour microenvironment that emphasises the roles of acetyl-CoA and the melatonergic pathway in shaping the dynamic intercellular metabolic interactions of the various cells within the tumour microenvironment. The potentiation of YY1 and GSK3β by O-GlcNAcylation will drive changes in metabolism in tumours and tumour microenvironment cells in association with their regulation of the melatonergic pathway. The emphasis on metabolic interactions across cell types in the tumour microenvironment provides novel future research and treatment directions.

scholarly journals Cancer Vaccines: Promising Therapeutics or an Unattainable Dream

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 668
Author(s):  
Howard Donninger ◽  
Chi Li ◽  
John W. Eaton ◽  
Kavitha Yaddanapudi
Keyword(s):  
Stem Cell ◽  
Immune System ◽  
Tumor Immunity ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Host Immune System ◽  
Tumor Type ◽  
Therapeutic Vaccines ◽  
Cancer Types ◽  
Prophylactic Vaccines

The advent of cancer immunotherapy has revolutionized the field of cancer treatment and offers cancer patients new hope. Although this therapy has proved highly successful for some patients, its efficacy is not all encompassing and several cancer types do not respond. Cancer vaccines offer an alternate approach to promote anti-tumor immunity that differ in their mode of action from antibody-based therapies. Cancer vaccines serve to balance the equilibrium of the crosstalk between the tumor cells and the host immune system. Recent advances in understanding the nature of tumor-mediated tolerogenicity and antigen presentation has aided in the identification of tumor antigens that have the potential to enhance anti-tumor immunity. Cancer vaccines can either be prophylactic (preventative) or therapeutic (curative). An exciting option for therapeutic vaccines is the emergence of personalized vaccines, which are tailor-made and specific for tumor type and individual patient. This review summarizes the current standing of the most promising vaccine strategies with respect to their development and clinical efficacy. We also discuss prospects for future development of stem cell-based prophylactic vaccines.

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