1. ¹Unit of Immunotherapy of Human Tumours, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
2. ²Unit of Immunobiotherapy of Solid Tumours, San Raffaele Scientific Institute, Milan, Italy
3. ³Department of Drug Research and Evaluation, Pharmacogenetic, Drug Resistance, and Experimental Therapeutic Section, Istituto Superiore di Sanità, Rome, Italy

Correspondence: L Rivoltini, Unit of Immunotherapy of Human Tumours, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, Milan 20133, Italy. Tel: 0+39 22390 3245; Fax: +39 22390 2154; E-mail: licia.rivoltini@istitutotumori.mi.it

Received 18 July 2007; Revised 7 September 2007; Accepted 7 September 2007; Published online 12 October 2007.

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.