Search results for "Tumor-Derived"

Technical Aspects for the Evaluation of Exosomes and Their Content

2017

Liquid biopsy is a precious source of exosomes, nanometer-sized vesicles (40–100 nm diameter) that play a relevant role in the cell-cell communication, strongly depending on the nature of the transported molecules (proteins, mRNAs, miRNAs, and lipids). Since a significant body of literature has demonstrated that exosomes released by cancer cells carry tumor-specific RNAs and proteins, they are widely considered very attractive targets for diagnostic application. This chapter focuses on the isolation and study of exosomes from liquid biopsies and summarizes the recent exosomal miRNA and protein profiling data supporting the potential role of tumor-derived exosomes as biomarkers and their pot…

A non-functional neoepitope specific CD8+ T-cell response induced by tumor derived antigen exposure in vivo

2018

Cancer-associated mutations, mostly single nucleotide variations, can act as neoepitopes and prime targets for effective anti-cancer T-cell immunity. T cells recognizing cancer mutations are critical for the clinical activity of immune checkpoint blockade (ICB) and they are potent vaccine antigens. High frequencies of mutation-specific T cells are rarely spontaneously induced. Hence, therapies that broaden the tumor specific T-cell response are of interest. Here, we analyzed neoepitope-specific CD8+ T-cell responses mounted either spontaneously or after immunotherapy regimens, which induce local tumor inflammation and cell death, in mice bearing tumors of the widely used colon carcinoma cel…

Angiogenic activity of breast cancer patients' monocytes reverted by combined use of systems modeling and experimental approaches.

2015

Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2-expressing monocytes (TEM) have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models, but the molecular basis of their pro-angiogenic activity are largely unknown. Moreover, differences in the pro-angiogenic activity between blood circulating and tumor infiltrated TEM in human patients has not been established to date, hindering the identification of specific targets for therapeutic intervention. In this work, we investigated these differences and the phenotypic reversal of breast tumor pro-angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean m…

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper.

2015

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics …

Tumor-derived lactic acid modulates dendritic cell activation and antigen expression.

2005

The tumor milieu can influence dendritic cell (DC) differentiation. We analyzed DC differentiation in a 3-dimensional tumor model and propose a new mechanism of DC modulation by the tumor environment. Monocytes were cultured in the presence of IL-4 and GM-CSF within multicellular tumor spheroids (MCTSs) generated from different tumor cell lines. Monocytes invaded the MCTSs and differentiated into tumor-associated dendritic cells (TADCs). The antigen expression was altered on TADCs independent of the culture conditions (immature/mature DCs, Langerhans cells) and IL-12 secretion was reduced. Supernatants of MCTSs could partially transfer the suppressive effect. Conditioned media from urotheli…

Colon cancer cell-derived exosomes modulate macrophage immunosuppressive phenotype associated to PD-L1 expression

Contribution of proteomics to understanding the role of tumor-derived exosomes in cancer progression: State of the art and new perspectives

2013

Exosomes are nanometer-sized vesicles (40-100 nm diameter) of endocytic origin released from different cell types under both normal and pathological conditions. They function as cell free messengers, playing a relevant role in the cell-cell communication that is strongly related to the nature of the molecules (proteins, mRNAs, miRNAs, and lipids) that they transport. Tumor cells actively shed exosomes into their surrounding microenvironment and growing evidence indicates that these vesicles have pleiotropic functions in the regulation of tumor progression, promoting immune escape, tumor invasion, neovascularization, and metastasis. During the last few years remarkable efforts have been made…

EXOSOMES DERIVED FROM METASTATIC COLON CANCER CELLS TRANSFER MALIGNANT PHENOTYPIC TRAITS TO SURROUNDING CELLS: THEIR EMERGING ROLE IN TUMOR HETEROGEN…

2018

Several studies have clearly demonstrated that within a heterogeneous tumor mass the inter-clonal cooperation between metastatic and non-metastatic cells can facilitate the tumor progression. Recent accumulating evidence has highlighted that tumor-derived exosomes (TDEs) play a relevant role as mediator of the inter-clonal collaborative cooperation affecting the properties of both tumor and non-tumor component. In this context, our goal was to understand if exosomes derived from highly metastatic cells may influence the behaviour of less aggressive tumor cells and the properties of endothelium. We found that metastatic SW620 cells transfer through exosomes (SW620Exos) their round/amoeboid p…

Extracellular vesicle DNA from human melanoma tissues contains cancer-specific mutations

2022

Liquid biopsies are promising tools for early diagnosis and residual disease monitoring in patients with cancer, and circulating tumor DNA isolated from plasma has been extensively studied as it has been shown to contain tumor-specific mutations. Extracellular vesicles (EVs) present in tumor tissues carry tumor-derived molecules such as proteins and nucleic acids, and thus EVs can potentially represent a source of cancer-specific DNA. Here we identified the presence of tumor-specific DNA mutations in EVs isolated from six human melanoma metastatic tissues and compared the results with tumor tissue DNA and plasma DNA. Tumor tissue EVs were isolated using enzymatic treatment followed by ultra…