A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal Activity
The latest advancements in oncology research are focused on autologous immune cell therapy. However, the effectiveness of this type of immunotherapy for cancer remediation is not equivalent for all patients or cancer types. This suggests the need for better preclinical screening models that more clo...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00857/full |
| _version_ | 1818595512545181696 |
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| author | Hilary Sherman Hannah J. Gitschier Ann E. Rossi |
| author_facet | Hilary Sherman Hannah J. Gitschier Ann E. Rossi |
| author_sort | Hilary Sherman |
| collection | DOAJ |
| description | The latest advancements in oncology research are focused on autologous immune cell therapy. However, the effectiveness of this type of immunotherapy for cancer remediation is not equivalent for all patients or cancer types. This suggests the need for better preclinical screening models that more closely recapitulate in vivo tumor biology. The established method for investigating tumoricidal activity of immunotherapies has been study of two-dimensional (2D) monolayer cultures of immortalized cancer cell lines or primary tumor cells in standard tissue culture vessels. Indeed, a proven means to examine immune cell migration and invasion are 2D chemotaxis assays in permeabilized supports or Boyden chambers. Nevertheless, the more in vivo-like three-dimensional (3D) multicellular tumor spheroids are quickly becoming the favored model to examine immune cell invasion and tumor cell cytotoxicity. Accordingly, we have developed a 3D immune oncology model by combining 96-well permeable support systems and 96-well low-attachment microplates. The use of the permeable support system enables assessment of immune cell migration, which was tested in this study as chemotactic response of natural killer NK-92MI cells to human stromal-cell derived factor-1 (SDF-1α). Immune invasion was assessed by measuring NK-92MI infiltration into lung carcinoma A549 cell spheroids that were formed in low-attachment microplates. The novel pairing of the permeable support system with low-attachment microplates permitted simultaneous investigation of immune cell homing, immune invasion of tumor spheroids, and spheroid cytotoxicity. In effect, the system represents a more comprehensive and in vivo-like immune oncology model that can be utilized for high-throughput study of tumoricidal activity. |
| first_indexed | 2024-12-16T11:17:12Z |
| format | Article |
| id | doaj.art-aa48d29ab70e44368919ffb6f5f56841 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T11:17:12Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-aa48d29ab70e44368919ffb6f5f568412022-12-21T22:33:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-04-01910.3389/fimmu.2018.00857336919A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal ActivityHilary ShermanHannah J. GitschierAnn E. RossiThe latest advancements in oncology research are focused on autologous immune cell therapy. However, the effectiveness of this type of immunotherapy for cancer remediation is not equivalent for all patients or cancer types. This suggests the need for better preclinical screening models that more closely recapitulate in vivo tumor biology. The established method for investigating tumoricidal activity of immunotherapies has been study of two-dimensional (2D) monolayer cultures of immortalized cancer cell lines or primary tumor cells in standard tissue culture vessels. Indeed, a proven means to examine immune cell migration and invasion are 2D chemotaxis assays in permeabilized supports or Boyden chambers. Nevertheless, the more in vivo-like three-dimensional (3D) multicellular tumor spheroids are quickly becoming the favored model to examine immune cell invasion and tumor cell cytotoxicity. Accordingly, we have developed a 3D immune oncology model by combining 96-well permeable support systems and 96-well low-attachment microplates. The use of the permeable support system enables assessment of immune cell migration, which was tested in this study as chemotactic response of natural killer NK-92MI cells to human stromal-cell derived factor-1 (SDF-1α). Immune invasion was assessed by measuring NK-92MI infiltration into lung carcinoma A549 cell spheroids that were formed in low-attachment microplates. The novel pairing of the permeable support system with low-attachment microplates permitted simultaneous investigation of immune cell homing, immune invasion of tumor spheroids, and spheroid cytotoxicity. In effect, the system represents a more comprehensive and in vivo-like immune oncology model that can be utilized for high-throughput study of tumoricidal activity.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00857/fullcancerimmune cell invasionimmune cell infiltrationimmune cell migrationimmune oncologyspheroid |
| spellingShingle | Hilary Sherman Hannah J. Gitschier Ann E. Rossi A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal Activity Frontiers in Immunology cancer immune cell invasion immune cell infiltration immune cell migration immune oncology spheroid |
| title | A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal Activity |
| title_full | A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal Activity |
| title_fullStr | A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal Activity |
| title_full_unstemmed | A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal Activity |
| title_short | A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal Activity |
| title_sort | novel three dimensional immune oncology model for high throughput testing of tumoricidal activity |
| topic | cancer immune cell invasion immune cell infiltration immune cell migration immune oncology spheroid |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00857/full |
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