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  • Sir Peter MacCallum Department of Oncology
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    An ultrastructural investigation of tumors undergoing regression mediated by immunotherapy

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    Author
    Westwood, JA; Ellis, S; Danne, J; Johnson, C; Oorschot, V; Ramm, G; Tscharke, DC; Davenport, AJ; Whisstock, JC; Darcy, PK; ...
    Date
    2017-12-29
    Source Title
    Oncotarget
    Publisher
    IMPACT JOURNALS LLC
    University of Melbourne Author/s
    Slaney, Clare; Ellis, Sarah; Darcy, Phillip; Kershaw, Michael
    Affiliation
    Sir Peter MacCallum Department of Oncology
    Metadata
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    Document Type
    Journal Article
    Citations
    Westwood, J. A., Ellis, S., Danne, J., Johnson, C., Oorschot, V., Ramm, G., Tscharke, D. C., Davenport, A. J., Whisstock, J. C., Darcy, P. K., Kershaw, M. H. & Slaney, C. Y. (2017). An ultrastructural investigation of tumors undergoing regression mediated by immunotherapy. ONCOTARGET, 8 (70), pp.115215-115229. https://doi.org/10.18632/oncotarget.23215.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255632
    DOI
    10.18632/oncotarget.23215
    Abstract
    While immunotherapy employing chimeric antigen receptor (CAR) T cells can be effective against a variety of tumor types, little is known about what happens within the tumor at an ultrastructural level during tumor regression. Here, we used transmission electron microscopy to investigate morphologic and cellular features of tumors responding to immunotherapy composed of adoptive transfer of dual-specific CAR T cells and a vaccine, supported by preconditioning irradiation and interleukin-2. Tumors responded rapidly, and large areas of cell death were apparent by 4 days after treatment. The pleomorphic and metabolically active nature of tumor cells and phagocytic activity of macrophages were apparent in electron microscopic images of tumors prior to treatment. Following treatment, morphologic features of various types of tumor cell death were observed, including apoptosis, paraptosis and necrosis. Large numbers of lipid droplets were evident in tumor cells undergoing apoptosis. Macrophages were the predominant leukocyte type infiltrating tumors before treatment. Macrophages decreased in frequency and number after treatment, whereas an increasing accumulation of neutrophils and T lymphocytes was observed following treatment. Phagocytic activity of macrophages and neutrophils was apparent, while T cells could be observed in close association with tumor cells with potential immunological synapses present. These observations highlight the cellular composition and ultrastructural appearance of tumors undergoing regression mediated by immunotherapy.

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