Apart from apoptotic bodies and ecto-somes, microvesicles that bud out of theplasma membrane, most types of cellsrelease exosomes when intracellular endo-somalmicrovesicularbodiesfusewiththeirplasmamembrane.Thislasttypeof vesicleswith attributed intercellular communicat-ing capabilities has acquired an enormousattentioninthepasttwodecades,especiallyfor their potential as disease biomarkersand/or their use as therapeutic vehicles.The intense study of their molecular com-position with special attention to miRNAhas led to the development of databaseslike Exocarta (http://www.exocarta.org/)(1); however, the way exosomes releasedfrom tumors (Tex) that may influence can-cer patient’s health is not yet completelyunderstood.The observation that exosome pro-duction and release is notably increasedwith tumor progression suggests that theymust play an active role in cancer (2,3). As tumors become more aggressive,heparanase activity is enhanced at leastin myeloma, lymphomas, or breast cancer,increasing both the number of exosomesreleased and the amount of syndecan-1,VEGF, and HGF molecules exposed ontheir surface (4).The advantages that Tex present for thedelivery of tumorigenic signaling mole-cules in relation to passive release into themedium are clear, especially for transportsacross long distances in the body. Firstly,encapsulation of labile molecules such asRNAs and proteins within lipid bilayersoffers them protection to degradation; sec-ondly, the surface landscape of the vesicleallows for the possibility of tissue or cellspecifictargetingandthirdlytheyaresuitedforsimultaneousmultiplemessagedeliveryallowing horizontal transfer of complexinformation from cancer to healthy cells.In addition to attenuation of antitu-mor immunity, Tex stimulate angiogen-esis, modulate stromal cells activity, andhelp on the extracellular matrix remod-eling contributing to the establishmentof a premetastatic niche and generat-ing suitable microenvironments at distantmetastatic sites (5). For example, Tex fromglioblastoma have the ability to potentiatetumor growth (6) and Tex from melanomacan directly tune a remote lymph nodeinto a microenvironment that facilitatesmelanoma growth and metastasis even inthe local absence of tumor cells (7). Theseand other similar studies suggest that Texactivities are mediated, at least in part,through the action of particular miRNAs,which presumably down regulate their tar-gettranscriptsinrecipientcells(8,9).Inter-estingly enough, Fabbri et al. have recentlyshowed that the Tex miR-21 and 29a mol-ecules can bind to toll-like receptor 7 and8 (TLR7 and 8) on immune cells and acti-vate them, leading to TLR-mediated NF-kB activation and secretion of prometasta-tic inflammatory cytokines (10, 11). Thisoffers an alternative mode of action forthe miR-mediated Tex paracrine effects inwhich miR act as aptamer-ligands. So, inaddition to Tex internalization Tex pro-tein, lipid, carbohydrate, or nucleic acidsurface receptors could interact with targetcell receptors to activate intracellular sig-naling; or, their surface proteins could becleaved by proteases, and the correspond-ing soluble fragments act as soluble lig-ands binding to targetcell surface receptors(12). In one case or another, Tex-mediatedactivities are a threat to patients workingtoward disease progression. Importantly,anti-cancer agents directed to inhibit DNAreplication or microtubule dynamics willresultinnocuoustoTex.Thisis,Texpresentthemselves,together with cancer stem cells,as a therapeutic resistant reservoir for theadvancement of the disease, and thereforeeffective cancer treatments must includetargeted inactivation and/or removal ofTex.On another side, however, exosomeshave emerged as potent stimulators ofimmune responses and from this pointof view as agents for cancer therapy.It has been recently showed that induc-tion of HSPs (heat shock proteins)-loadedTex occurred when hepatocarcinoma cellswere treated with chemotherapeutics suchas paclitaxel or carboplatin. These Texreleased by treated cancer cells con-ferred superior immunogenicity in induc-ing HSPs-specific NK cell responses (13).Exosomes can carry a broad variety ofimmune-stimulatorymoleculesdependingon the cell of origin and