Molecular pathways: tumor-derived microvesicles and their interactions with immune cells in vivo

Abstract

Cancer is not merely a cell-intrinsic genetic disease but also the result of complex cell-extrinsic interactions with host components, including immune cells. For example, effector T lymphocytes and natural killer cells are thought to participate in an immunosurveillance process, which eliminates neoplastic cells, whereas regulatory T lymphocytes and some myeloid cells, including macrophages, can create a milieu that prevents antitumor activity, supports tumor growth, and reduces survival of the host. Increasing evidence supports the notion that carcinoma cells communicate with immune cells directly, both within and away from the tumor stroma, and that this process fosters suppression of immunosurveillance and promotes tumor outgrowth. An important mode of communication between carcinoma cells and immune cells may involve tumor-derived microvesicles (tMV), also known as exosomes, ectosomes, or microparticles. These microvesicles carry lipids, proteins, mRNAs and microRNAs and travel short or long distances to deliver undegraded and undiluted material to other cells. Here, we consider the capacity of tMVs to control tumor-associated immune responses and highlight the known and unknown actions of tMVs in vivo. We also discuss why microvesicles may play a role in cancer diagnostics and prognostics and how they could be harnessed for anticancer therapy.

Fig. 1

A sketch depicting MV tropism in vivo in cancer-bearing hosts. 1: Both tumor and host cells produce MVs that may affect other cell types locally, either by surface binding (MVs acting as ligand clustering agents) and/or by transferring bioactive material to target cells (horizontal transfer of proteins, RNAs and lipids). MVs from host cells may provide trophic functions by nurturing tumor cells; 2: tMVs can be drained into lymphatics and shape anti-tumor immune responses; 3: tMVs can circulate to distant organs like bone marrow and alter hematopoiesis. Blood MVs can be harnessed as surrogate tumor cells for diagnostic/prognostic purposes.