CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling
Abstract Background CD137 is a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis, has not been studied. Methods Foxp3+ and CD8+ T cells in GCs were investigated using immunohistochemistry (IHC). CD137 expression in GCs was det...
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01605-0 |
| _version_ | 1818149140170801152 |
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| author | Ben-Shun Hu Tian Tang Jun-Li Jia Bi-Chen Xie Tie-Long Wu Ying-Yue Sheng Yu-Zheng Xue Hua-Min Tang |
| author_facet | Ben-Shun Hu Tian Tang Jun-Li Jia Bi-Chen Xie Tie-Long Wu Ying-Yue Sheng Yu-Zheng Xue Hua-Min Tang |
| author_sort | Ben-Shun Hu |
| collection | DOAJ |
| description | Abstract Background CD137 is a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis, has not been studied. Methods Foxp3+ and CD8+ T cells in GCs were investigated using immunohistochemistry (IHC). CD137 expression in GCs was detected using flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cell proliferation and p65 expression was examined using flow cytometry. P65 nuclear translocation was analyzed using IF. IL-10, TGF-β, IFN-γ, perforin and granzyme B were detected using real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with a CD137 agonist in vitro. Apoptosis of primary GC cells was detected using flow cytometry. Results Our data demonstrated that GC tumors showed characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. The CD137 agonist promoted CD8+ T cell proliferation and increased the secretion of IFN-γ, perforin and granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that the CD137 agonist induced NF-κB nuclear translocation in CD8+ T cells. Conclusion Our results demonstrated that a CD137 agonist induced primary GC cell apoptosis by enhancing CD8+ T cells via activation of NF-κB signaling. |
| first_indexed | 2024-12-11T13:02:18Z |
| format | Article |
| id | doaj.art-c78912583e0646aea3dbb9370b9dfeac |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-11T13:02:18Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-c78912583e0646aea3dbb9370b9dfeac2022-12-22T01:06:26ZengBMCCancer Cell International1475-28672020-10-0120111410.1186/s12935-020-01605-0CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signalingBen-Shun Hu0Tian Tang1Jun-Li Jia2Bi-Chen Xie3Tie-Long Wu4Ying-Yue Sheng5Yu-Zheng Xue6Hua-Min Tang7School of Basic Medical Sciences, Nanjing Medical UniversitySchool of Basic Medical Sciences, Nanjing Medical UniversitySchool of Basic Medical Sciences, Nanjing Medical UniversityDepartment of Pathology, Affiliated Hospital of Jiangnan UniversityDepartment of Gastroenterology, Affiliated Hospital of Jiangnan UniversityDepartment of Gastroenterology, Affiliated Hospital of Jiangnan UniversityDepartment of Gastroenterology, Affiliated Hospital of Jiangnan UniversitySchool of Basic Medical Sciences, Nanjing Medical UniversityAbstract Background CD137 is a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis, has not been studied. Methods Foxp3+ and CD8+ T cells in GCs were investigated using immunohistochemistry (IHC). CD137 expression in GCs was detected using flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cell proliferation and p65 expression was examined using flow cytometry. P65 nuclear translocation was analyzed using IF. IL-10, TGF-β, IFN-γ, perforin and granzyme B were detected using real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with a CD137 agonist in vitro. Apoptosis of primary GC cells was detected using flow cytometry. Results Our data demonstrated that GC tumors showed characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. The CD137 agonist promoted CD8+ T cell proliferation and increased the secretion of IFN-γ, perforin and granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that the CD137 agonist induced NF-κB nuclear translocation in CD8+ T cells. Conclusion Our results demonstrated that a CD137 agonist induced primary GC cell apoptosis by enhancing CD8+ T cells via activation of NF-κB signaling.http://link.springer.com/article/10.1186/s12935-020-01605-0CD137Gastric cancerCD8+ T cellsImmune microenvironmentImmune checkpoint |
| spellingShingle | Ben-Shun Hu Tian Tang Jun-Li Jia Bi-Chen Xie Tie-Long Wu Ying-Yue Sheng Yu-Zheng Xue Hua-Min Tang CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling Cancer Cell International CD137 Gastric cancer CD8+ T cells Immune microenvironment Immune checkpoint |
| title | CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling |
| title_full | CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling |
| title_fullStr | CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling |
| title_full_unstemmed | CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling |
| title_short | CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8+ T cells via NF-κB signaling |
| title_sort | cd137 agonist induces gastric cancer cell apoptosis by enhancing the functions of cd8 t cells via nf κb signaling |
| topic | CD137 Gastric cancer CD8+ T cells Immune microenvironment Immune checkpoint |
| url | http://link.springer.com/article/10.1186/s12935-020-01605-0 |
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