Tumor-Released Microvesicles as Vehicles of Immunosuppression

Abstract

Tumor-released microvesicles, or exosomes, which are abundant in the body fluids of patients with cancer, are likely to be involved in tumor progression. We recently showed that microvesicles released by human melanoma and colorectal carcinoma cells can promote the differentiation of monocytes to myeloid-derived suppressor cells which support tumoral growth and immune escape. These findings underscore an important role for these extracellular organelles in remodeling tumor-stromal interactions to promote malignancy.

Exosomes Released by Melanoma Cells Prepare Sentinel Lymph Nodes for Tumor Metastasis

“…Induction of TNF-a therefore signifies simultaneous upregulation of angiogenic and immunosuppressive activities by native melanoma exosomes in the lymph node microenvironment. This supports our previous work showing simultaneous induction of angiogenesis and immunosuppressive factors (GM-CSF and TNF-a) by melanoma exosomes (15) and is consistent with other in vitro reports showing melanoma microvesicle mediated "counterattack" of antitumor T-cells (8) and induction of MDSCs (11,46) which suppress antitumor T-cell function (45).…”

Tumour-released exosomes and their implications in cancer immunity

“…46,47 Other immune effectors, such as for instance natural killer cells, are not spared from these negative influences as they lose their cytolytic potential, through the downmodulation of perforin expression, upon encounter with tumour-secreted microvesicles. 48 These data, together with those collected by other groups, 41,49 suggest that exosomes might also act as a vehicle for suppressive signals and have negative effects on antitumour immune responses. This hypothesis appears to be in contrast with the initial evidence of immunogenicity described for tumour exosomes cross-presented by DCs.…”

“…16 The fact that the hallmark alterations induced by tumour microvesicles on host cells in vitro can also be found in immune cells isolated from cancer patients supports the hypothesis that these negative loops can actually be established in vivo as well. 41,42 As a further proof of the pleiotropic effect of tumour-secreted exosomes, it should be mentioned that tumour exosomes can also interfere directly with T cell effector functions. Indeed, we have recently shown that the • Exosome-transported molecules…”

Role of extracellular membrane vesicles in the pathogenesis of various diseases, including cancer, renal diseases, atherosclerosis, and arthritis

“…Angiogenic molecules such as TF, 30,34 VEGF, 30,35 cell surface adhesion molecular markers, [36][37][38] immune suppressing cytokines, 39 miRNA, 35 sphingomyelin, 40 tumor surface antigens [41][42][43] DCs, endothelial cells, epithelial cells, hematopoietic cells, platelets, tumor cells Andre et al, 44 Choi et al, 36 Dolo et al, 45 Dolo et al, 38 Dvorak, 30 Giusti et al, 37 Kim et al, 40 Koga et al, 43 Mitchell et al, 41 Osterud, 34 Skog et al, 35 Taraboletti et al, 46 Valenti et al 39 Bacterial infections Cytokines, [47][48][49] glycoproteolipids, 50 lipopolysaccharides, 50 quorum-sensing agents, 51 virulence factors, 52,53 TLR ligands 48,50 Pathogenic bacteria, host macrophages Alaniz et al, 49 Bhatnagar et al, 50 Ismail et al, 47 Kuehn and Kesty, 48 Li et al, 54 Nowotny et al, 52 Mashburn and hip). OA usually begins in the middle age and gradually worsens with age.…”

“…An important function of tumor cell-generated MVs is to evade host immunity. 39 TCMVs have diameters in the size range of 30-100 nm, 39 and are generated by fusion of endosomal membranes (eg, from multivesicular bodies 87 ) with the plasma membrane, which then exfoliates PM-derived MVs with various functions, including suppression of antitumor cell immunity 39 ( Table 2). TCMVs also promote tissue invasion by transport and release of proteases, which digest host tissues at the site of invasion.…”