Emerging role of tumor-derived extracellular vesicles in T cell suppression and dysfunction in the tumor microenvironment


Posted: 2021-10-13 19:00:00
Review J Immunother Cancer . 2021 Oct;9(10):e003217. doi: 10.1136/jitc-2021-003217. Affiliations Expand Affiliations 1 Biology, Saint Louis University, Saint Louis, Missouri, USA. 2 Biology, Saint Louis University, Saint Louis, Missouri, USA yuqi.wang@slu.edu guangyong.peng@health.slu.edu. 3 Internal Medicine, Saint Louis University, Saint Louis, Missouri, USA yuqi.wang@slu.edu guangyong.peng@health.slu.edu. Item in Clipboard Review Feiya Ma et al. J Immunother Cancer. 2021 Oct. Show details Display options Display options Format J Immunother Cancer . 2021 Oct;9(10):e003217. doi: 10.1136/jitc-2021-003217. Affiliations 1 Biology, Saint Louis University, Saint Louis, Missouri, USA. 2 Biology, Saint Louis University, Saint Louis, Missouri, USA yuqi.wang@slu.edu guangyong.peng@health.slu.edu. 3 Internal Medicine, Saint Louis University, Saint Louis, Missouri, USA yuqi.wang@slu.edu guangyong.peng@health.slu.edu. Item in Clipboard CiteDisplay options Display options Format Abstract Immunotherapeutic drugs including immune checkpoint blockade antibodies have been approved to treat patients in many types of cancers. However, some patients have little or no reaction to the immunotherapy drugs. The mechanisms underlying resistance to tumor immunotherapy are complicated and involve multiple aspects, including tumor-intrinsic factors, formation of immunosuppressive microenvironment, and alteration of tumor and stromal cell metabolism in the tumor microenvironment. T cell is critical and participates in every aspect of antitumor response, and T cell dysfunction is a severe barrier for effective immunotherapy for cancer. Emerging evidence indicates that extracellular vesicles (EVs) secreted by tumor is one of the major factors that can induce T cell dysfunction. Tumor-derived EVs are widely distributed in serum, tissues, and the tumor microenvironment of patients with cancer, which serve as important communication vehicles for cancer cells. In addition, tumor-derived EVs can carry a variety of immune suppressive signals driving T cell dysfunction for tumor immunity. In this review, we explore the potential mechanisms employed by tumor-derived EVs to control T cell development and effector function within the tumor microenvironment. Especially, we focus on current understanding of how tumor-derived EVs molecularly and metabolically reprogram T cell fates and functions for tumor immunity. In addition, we discuss potential translations of targeting tumor-derived EVs to reconstitute suppressive tumor microenvironment or to develop antigen-based vaccines and drug delivery systems for cancer immunotherapy. Keywords: adaptive immunity; immune evation; immune tolerance; immunotherapy; tumor microenvironment. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Conflict of interest statement Competing interests: No, there are no competing interests. Publication types [x] Cite Copy Format: Send To [x]

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