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Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments

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Abstract

Cancer cells, both in vivo and in vitro, have been demonstrated to release membranous structures, defined as microvesicles or exosomes, consisting of an array of macromolecules derived from the originating cells, including proteins, lipids, and nucleic acids. While only recently have the roles of these vesicular components in intercellular communication become elucidated, significant evidence has demonstrated that tumor exosomes can exert a broad array of detrimental effects on the immune system—ranging from apoptosis of activated cytotoxic T cells to impairment of monocyte differentiation into dendritic cells, to induction of myeloid-suppressive cells and T regulatory cells. Immunosuppressive exosomes of tumor origin can be found within neoplastic lesions and in biologic fluids from cancer patients, implying a potential role of these pathways in in vivo tumor progression and systemic paraneoplastic syndromes. Through the expression of molecules involved in angiogenesis promotion, stromal remodeling, signaling pathway activation through growth factor/receptor transfer, chemoresistance, and genetic intercellular exchange, tumor exosomes could represent a central mediator of the tumor microenvironment. By understanding the nature of these tumor-derived exosomes/microvesicles and their roles in mediating cancer progression and modulating the host immune response will significantly impact therapeutic approaches targeting exosomes.

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Authors and Affiliations

  1. Department of Obstetrics, Gynecology and Women’s Health and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA

    Douglas D. Taylor & Cicek Gercel-Taylor

  2. Division of Gynecologic Oncology, University of Louisville, Clinical Translational Research Building, 505 S. Hancock St., Room 316, Louisville, KY, 40202, USA

    Douglas D. Taylor

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Correspondence to Douglas D. Taylor.

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This article is published as part of the Special Issue on Small Vesicles as Immune Modulators.

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Taylor, D.D., Gercel-Taylor, C. Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol 33, 441–454 (2011). https://doi.org/10.1007/s00281-010-0234-8

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