Oncotarget

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Exosomes in melanoma: a role in tumor progression, metastasis and impaired immune system activity

Marco Tucci _, Francesco Mannavola, Anna Passarelli, Luigia Stefania Stucci, Mauro Cives and Franco Silvestris

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Oncotarget. 2018; 9:20826-20837. https://doi.org/10.18632/oncotarget.24846

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Abstract

Marco Tucci1, Francesco Mannavola1, Anna Passarelli1, Luigia Stefania Stucci1, Mauro Cives1 and Franco Silvestris1

1Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy

Correspondence to:

Marco Tucci, email: marco.tucci@uniba.it

Keywords: exosomes; melanoma; immune system

Received: January 26, 2018     Accepted: March 07, 2018     Published: April 17, 2018

ABSTRACT

Exosomes (Exo) are small vesicles produced by melanoma cells and the accessory cells of the tumor microenvironment. They emerge via both classical and direct pathways and actively participate in tumor colonisation of distant tissues. The proteins, nucleic acids, cytokines and growth factors engulfed by Exo are transferred to recipient cells, where they drive numerous functions required for the tumor escape from immune system control and tumor progression. By positively or negatively modulating immune cell properties, Exo provoke immune suppression and, in turn, defective dendritic cell (DC) functions. Together, these effects limit the cytotoxicity of T-cells and expand both T-regulatory and myeloid-derived suppressor populations. They also hinder perforin and granzyme production by natural killer cells. Finally, Exo also control the organotropism of melanoma cells. The distinct phenotypic properties of Exo can be exploited both for diagnostic purposes and in the early identification of melanoma patients likely to respond to immunotherapy. The potential therapeutic application of Exo derived from DCs has been demonstrated in vaccination trials, which showed an increase in anti-melanoma activity with respect to circulating tumor cells. However, additional studies are required before Exo can be effectively used in diagnostic and therapeutic applications in melanoma.


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PII: 24846