Tumor-derived exosomes as dendritic cell modulators

Roberta Valenti, Veronica Huber, Paola Filipazzi, Manuela Iero, Giorgio Parmiani, Licia Rivoltini

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Cancer cells constitutively release endosome-derived microvesicles, also called 'exosomes', carrying a broad array of molecular determinants involved in the remodeling of the peritumoral microenvironment. This recently defined alternative mechanism of intercellular communication is exploited by tumor cells to favor their own growth and survival through the delivery of detrimental signals to the host's innate and adaptive immune system. Initially described for their ability to transfer tumor antigens to dendritic cells in a protected and highly immunogenic membrane-embedded form, tumor-derived exosomes have been more recently hinted to exert immunosuppressive effects on the development of antitumor immune responses at different levels. In particular, due to the transport of FasL and TRAIL pro-apoptotic molecules, exosomes derived from different tumor histotypes proved to induce programmed cell death of activated antitumor-specific T cells. On the other hand, the same microvesicles seem to mine immune-mediated recognition and elimination of cancer cells since their initial stages, regarding antigen uptake and presentation by dendritic cells. As reported herein, cancer patients display several phenotypic and functional defects in this cell subset, together with a more generalized dysfunction of the myeloid cell compartment, due to the tumor-driven expansion and activation of the so-called 'myeloid suppressor cells'. A possible involvement of tumor-derived exosomes in the disruption of the homeostasis of the antigen-presenting cell compartment in cancer patients has been recently suggested by a series of experimental evidences, as it will be mainly discussed in this chapter.

Original languageEnglish
Title of host publicationDendritic Cells in Cancer
PublisherSpringer US
Pages119-128
Number of pages10
ISBN (Print)9780387886107
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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