Abstract
Tumour cells release vesicular structures, defined as microvesicles or exosomes, carrying a large array of proteins from their originating cell. The expression of antigenic molecules recognized by T cells has originally suggested a role for these organelles as a cell-free antigen source for anticancer vaccines. However, recent evidence shows that tumour exosomes may also exert a broad array of detrimental effects on the immune system, ranging from apoptosis in activated antitumour T cells to impairment of monocyte differentiation into dendritic cells and induction of myeloid suppressive cells. Immunosuppressive exosomes of tumour origin can be found in neoplastic lesions and sera from cancer patients, implying a potential role of this pathway in in vivo tumour progression. Through the expression of molecules involved in angiogenesis promotion, stromal remodelling, delivery of signalling pathways through growth factor/receptor transfer, chemoresistance and genetic intercellular exchange, tumour exosomes could represent a versatile tool for moulding host environment. Hence, their secretion by neoplastic cells may in the future become a novel pathway to target for therapeutic intervention in cancer patients.
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Abbreviations
- APC:
-
antigen-presenting cell
- DC:
-
dendritic cell
- DEX:
-
DC exosome
- ESCRT:
-
endosomal sorting complexes required for transport
- HSP:
-
heat-shock protein
- LN:
-
lymph node
- MMP:
-
matrix metalloproteinase
- MSC:
-
myeloid suppressor cell
- MVB:
-
multivesicular body
- PPI:
-
proton pump inhibitor
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Acknowledgements
We are grateful to Drs. Fabio Castiglioni and Erica Dugnani (Unit of Molecular Biology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy) for the excellent graphical support, and to Dr. Antonello Villa (MIA Consortium, University of Bicocca, Milan, Italy) for scanning electron microscopy images. This work was supported by grants from the European Community Cancer Immunology and Immunotherapy contract no. 518234), the Italian Ministry of Industry, University and Research (Rome, Italy: grant FIRB RBNE017B4C), the Italian Association for Cancer Research. R Valenti was supported by a scholarship from the Foundation for Cancer Research (Milan, Italy).
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Iero, M., Valenti, R., Huber, V. et al. Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ 15, 80–88 (2008). https://doi.org/10.1038/sj.cdd.4402237
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DOI: https://doi.org/10.1038/sj.cdd.4402237
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