Gastrospheres as a Model of Gastric Cancer Stem Cells Skew Th17/Treg Balance toward Antitumor Th17 Cells
Background. Gastrosphere, an enriched cellular population with stem-like properties believed to be responsible for an escape from immune-mediated destruction. Th17 and Treg cells play a major role in gastric cancer; however, their interaction with gastrospheres remained elusive. Method. Peripheral b...
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| Format: | Article |
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Wiley
2020-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/6261814 |
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| author | Alaleh Rezalotfi Ghasem Solgi Marzieh Ebrahimi |
| author_facet | Alaleh Rezalotfi Ghasem Solgi Marzieh Ebrahimi |
| author_sort | Alaleh Rezalotfi |
| collection | DOAJ |
| description | Background. Gastrosphere, an enriched cellular population with stem-like properties believed to be responsible for an escape from immune-mediated destruction. Th17 and Treg cells play a major role in gastric cancer; however, their interaction with gastrospheres remained elusive. Method. Peripheral blood mononuclear cells were isolated from healthy donors and were cultured with conditioned media of MKN-45 (parental) cells as well as gastrospheres’ conditioned media in the context of mixed lymphocyte reaction and in the presence of anti-CD3/CD28 beads. The proliferation was evaluated using CFSE staining; the percentages of CD4+CD25+FoxP3+ Treg and CD4+IL-17+ Th17 cells and IFN-γ+cells and the production of IL-17, TGF-β, and IL-10 were assessed by flow cytometry and ELISA, respectively. Finally, the cytotoxic potential of induced immune cells was measured by examining the secretion of lactate dehydrogenase from target cells. Results. The results revealed a decreased expansion of PBMCs postexposure to gastrospheres’ conditioned medium which was concomitant with an increased percentage of Th17 and an enhanced Th17 to Treg ratio. The conditioned media of gastrospheres enhanced the secretion of IL-10 and IL-17 and decreased TGF-β. Interestingly, immune cells induced by gastrospheres showed significant cytotoxicity in terms of producing IFN-γ and death induction in target cells. All these changes were related to the upregulation of IL-6, IL-10, and IL-22 in gastrospheres compared to parental cells. Conclusion. Our study showed that the condition media of gastrospheres can potentially induce Th17 with increasing in their cytotoxic effect. Based on our knowledge, the present study is the first study that emphasizes the role of gastrospheres in the induction of antitumor Th17 cells. However, it should be confirmed with complementary studies in vivo. |
| format | Article |
| id | doaj-art-43677136fa704de09149b443add6df32 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-43677136fa704de09149b443add6df322025-02-03T06:05:28ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/62618146261814Gastrospheres as a Model of Gastric Cancer Stem Cells Skew Th17/Treg Balance toward Antitumor Th17 CellsAlaleh Rezalotfi0Ghasem Solgi1Marzieh Ebrahimi2Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranBackground. Gastrosphere, an enriched cellular population with stem-like properties believed to be responsible for an escape from immune-mediated destruction. Th17 and Treg cells play a major role in gastric cancer; however, their interaction with gastrospheres remained elusive. Method. Peripheral blood mononuclear cells were isolated from healthy donors and were cultured with conditioned media of MKN-45 (parental) cells as well as gastrospheres’ conditioned media in the context of mixed lymphocyte reaction and in the presence of anti-CD3/CD28 beads. The proliferation was evaluated using CFSE staining; the percentages of CD4+CD25+FoxP3+ Treg and CD4+IL-17+ Th17 cells and IFN-γ+cells and the production of IL-17, TGF-β, and IL-10 were assessed by flow cytometry and ELISA, respectively. Finally, the cytotoxic potential of induced immune cells was measured by examining the secretion of lactate dehydrogenase from target cells. Results. The results revealed a decreased expansion of PBMCs postexposure to gastrospheres’ conditioned medium which was concomitant with an increased percentage of Th17 and an enhanced Th17 to Treg ratio. The conditioned media of gastrospheres enhanced the secretion of IL-10 and IL-17 and decreased TGF-β. Interestingly, immune cells induced by gastrospheres showed significant cytotoxicity in terms of producing IFN-γ and death induction in target cells. All these changes were related to the upregulation of IL-6, IL-10, and IL-22 in gastrospheres compared to parental cells. Conclusion. Our study showed that the condition media of gastrospheres can potentially induce Th17 with increasing in their cytotoxic effect. Based on our knowledge, the present study is the first study that emphasizes the role of gastrospheres in the induction of antitumor Th17 cells. However, it should be confirmed with complementary studies in vivo.http://dx.doi.org/10.1155/2020/6261814 |
| spellingShingle | Alaleh Rezalotfi Ghasem Solgi Marzieh Ebrahimi Gastrospheres as a Model of Gastric Cancer Stem Cells Skew Th17/Treg Balance toward Antitumor Th17 Cells Journal of Immunology Research |
| title | Gastrospheres as a Model of Gastric Cancer Stem Cells Skew Th17/Treg Balance toward Antitumor Th17 Cells |
| title_full | Gastrospheres as a Model of Gastric Cancer Stem Cells Skew Th17/Treg Balance toward Antitumor Th17 Cells |
| title_fullStr | Gastrospheres as a Model of Gastric Cancer Stem Cells Skew Th17/Treg Balance toward Antitumor Th17 Cells |
| title_full_unstemmed | Gastrospheres as a Model of Gastric Cancer Stem Cells Skew Th17/Treg Balance toward Antitumor Th17 Cells |
| title_short | Gastrospheres as a Model of Gastric Cancer Stem Cells Skew Th17/Treg Balance toward Antitumor Th17 Cells |
| title_sort | gastrospheres as a model of gastric cancer stem cells skew th17 treg balance toward antitumor th17 cells |
| url | http://dx.doi.org/10.1155/2020/6261814 |
| work_keys_str_mv | AT alalehrezalotfi gastrospheresasamodelofgastriccancerstemcellsskewth17tregbalancetowardantitumorth17cells AT ghasemsolgi gastrospheresasamodelofgastriccancerstemcellsskewth17tregbalancetowardantitumorth17cells AT marziehebrahimi gastrospheresasamodelofgastriccancerstemcellsskewth17tregbalancetowardantitumorth17cells |