We did read with great interest the recent review published by Ichim et al on the potential role of tumor exosomes as immune escape mechanism [1], and we were pleased to see that the authors shared our original idea that these organelles may represent a crucial tool of immunosuppression in cancer [2, 3]. Indeed, although tumor cells are well acknowledged to affect immune functions through the release of diverse soluble factors or cellto-cell contact mediated mechanisms [4, 5], the involvement of alternative pathways based on the secretion of membrane microvesicles has been so far largely unappreciated [6]. Exosomes are endosome-derived organelles of 50–100 nm size, actively secreted by virtually all cell types through an exocytosis pathway that is used under normal as well as pathological conditions [6]. Their first description can be attributed to the biochemist Rose Johnstone, who reported in her 1980s investigations about these lipid-encased particles produced as a mechanism for shedding of specific membrane functions during reticulocyte maturation [7]. Since then, these curious microvesicles lingered in obscurity, although several reports kept referring to exosomes as potential pathway utilized by different cell types to eliminate cellular material or establish intercellular cross-talk [8]. Finally in 1996 these microparticles were recognized for their central role in antigen presentation with the work of Graça Raposo and Hans Geuze of Utrecht University in the Netherlands, who reported that exosomes secreted by B cells could promote T cell cross-priming through the expression of HLA/peptide complexes [6]. Based on these and following observations about the role of exosomes in antigen presentation, the exacerbated production of these vesicles by tumor cells was initially welcomed as a process potentially involved in the induction and maintenance of tumor immunity [9]. Indeed, the expression of a large panel of tumor proteins with antigenic properties, like MelanA/Mart-1 and gp100 in melanoma-derived exosomes, and CEA and HER2 in exosomes produced by carcinoma cells [9-11], supported the role of these organelles as cell-free source of tumor antigens for T cell priming and paved the way to clinical trials based on vaccination with tumor exosomes in patients with advanced disease [12].

However, following studies from several groups including ours have progressively suggested that these vesicles, being close replicas of the originating cancer cells, could transport not only antigenic material but also molecules responsible for the detrimental effects exerted by tumor cells on the immune system [6, 13, 14].