An ultrastructural investigation of tumors undergoing regression mediated by immunotherapy

Jennifer A. Westwood, Sarah Ellis, Jill Danne, Chad Johnson, Viola Oorschot, Georg Ramm, David C. Tscharke, Alexander J. Davenport, James C. Whisstock, Phillip K. Darcy, Michael H. Kershaw, Clare Y. Slaney

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)115215-115229
Number of pages15
JournalOncotarget
Volume8
Issue number70
DOIs
Publication statusPublished - 14 Dec 2017

Keywords

  • Apoptosis
  • Breast cancer
  • Cancer vaccine
  • Electron microscopy
  • Tumor regression

Cite this

Westwood, J. A., Ellis, S., Danne, J., Johnson, C., Oorschot, V., Ramm, G., ... Slaney, C. Y. (2017). An ultrastructural investigation of tumors undergoing regression mediated by immunotherapy. Oncotarget, 8(70), 115215-115229. https://doi.org/10.18632/oncotarget.23215
Westwood, Jennifer A. ; Ellis, Sarah ; Danne, Jill ; Johnson, Chad ; Oorschot, Viola ; Ramm, Georg ; Tscharke, David C. ; Davenport, Alexander J. ; Whisstock, James C. ; Darcy, Phillip K. ; Kershaw, Michael H. ; Slaney, Clare Y. / An ultrastructural investigation of tumors undergoing regression mediated by immunotherapy. In: Oncotarget. 2017 ; Vol. 8, No. 70. pp. 115215-115229.
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Westwood, JA, Ellis, S, Danne, J, Johnson, C, Oorschot, V, Ramm, G, Tscharke, DC, Davenport, AJ, Whisstock, JC, Darcy, PK, Kershaw, MH & Slaney, CY 2017, 'An ultrastructural investigation of tumors undergoing regression mediated by immunotherapy', Oncotarget, vol. 8, no. 70, pp. 115215-115229. https://doi.org/10.18632/oncotarget.23215

An ultrastructural investigation of tumors undergoing regression mediated by immunotherapy. / Westwood, Jennifer A.; Ellis, Sarah; Danne, Jill; Johnson, Chad; Oorschot, Viola; Ramm, Georg; Tscharke, David C.; Davenport, Alexander J.; Whisstock, James C.; Darcy, Phillip K.; Kershaw, Michael H.; Slaney, Clare Y.

In: Oncotarget, Vol. 8, No. 70, 14.12.2017, p. 115215-115229.

Research output: Contribution to journalArticleResearchpeer-review

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