Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour Growth
The dysfunction of natural killer (NK) cells has been increasingly reported in malignancies, especially in solid tumours. Mesenchymal stem cells (MSCs) exhibit pleiotropic functions that include mediating immune cell exhaustion which is implicated in cancer progression. However, the association of M...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2021/9989790 |
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| author | Shuwei Guo Chao Huang Fengfeng Han Bin Chen Ying Ding Yuanyuan Zhao Zhihong Chen Shaodi Wen Mei Wang Bo Shen Wei Zhu |
| author_facet | Shuwei Guo Chao Huang Fengfeng Han Bin Chen Ying Ding Yuanyuan Zhao Zhihong Chen Shaodi Wen Mei Wang Bo Shen Wei Zhu |
| author_sort | Shuwei Guo |
| collection | DOAJ |
| description | The dysfunction of natural killer (NK) cells has been increasingly reported in malignancies, especially in solid tumours. Mesenchymal stem cells (MSCs) exhibit pleiotropic functions that include mediating immune cell exhaustion which is implicated in cancer progression. However, the association of MSCs derived from gastric cancer (gastric cancer mesenchymal stem cells: GCMSCs) with the dysfunction of NK cells remains poorly understood. In this study, we demonstrated that GCMSCs effectively contributed to the exhaustion of NK cells through the release of soluble factors. Furthermore, passivation of the antitumour effect in NK cells was closely associated with their dysfunctional state. The GCMSC-conditioned medium prevented the frequency and effector function of infiltrating NK cells in tumour-bearing mouse models, thus promoting tumour growth. Mechanistically, mammalian target of rapamycin (mTOR) signalling, a critical regulator of cellular metabolism that mediates the function of immune cells, was inhibited in NK cells treated with GCMSCs. However, the checkpoint receptor PD-1 was still present at minimal levels with or without GCMSCs. The study results revealed that GCMSCs contributed to dysfunctional NK cells involved at least partially in the inhibition of mTOR signalling, suggesting potential directions for NK cell-based cancer immunotherapy. |
| format | Article |
| id | doaj-art-b52b72073e904387b185e5e74a800444 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-b52b72073e904387b185e5e74a8004442025-02-03T07:23:59ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/99897909989790Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour GrowthShuwei Guo0Chao Huang1Fengfeng Han2Bin Chen3Ying Ding4Yuanyuan Zhao5Zhihong Chen6Shaodi Wen7Mei Wang8Bo Shen9Wei Zhu10School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaSchool of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaSchool of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaSchool of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaSchool of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaSchool of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaDepartment of Gastrointestinal Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, ChinaDepartment of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, ChinaSchool of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaDepartment of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, ChinaSchool of Medicine, Jiangsu University, Zhenjiang, Jiangsu, ChinaThe dysfunction of natural killer (NK) cells has been increasingly reported in malignancies, especially in solid tumours. Mesenchymal stem cells (MSCs) exhibit pleiotropic functions that include mediating immune cell exhaustion which is implicated in cancer progression. However, the association of MSCs derived from gastric cancer (gastric cancer mesenchymal stem cells: GCMSCs) with the dysfunction of NK cells remains poorly understood. In this study, we demonstrated that GCMSCs effectively contributed to the exhaustion of NK cells through the release of soluble factors. Furthermore, passivation of the antitumour effect in NK cells was closely associated with their dysfunctional state. The GCMSC-conditioned medium prevented the frequency and effector function of infiltrating NK cells in tumour-bearing mouse models, thus promoting tumour growth. Mechanistically, mammalian target of rapamycin (mTOR) signalling, a critical regulator of cellular metabolism that mediates the function of immune cells, was inhibited in NK cells treated with GCMSCs. However, the checkpoint receptor PD-1 was still present at minimal levels with or without GCMSCs. The study results revealed that GCMSCs contributed to dysfunctional NK cells involved at least partially in the inhibition of mTOR signalling, suggesting potential directions for NK cell-based cancer immunotherapy.http://dx.doi.org/10.1155/2021/9989790 |
| spellingShingle | Shuwei Guo Chao Huang Fengfeng Han Bin Chen Ying Ding Yuanyuan Zhao Zhihong Chen Shaodi Wen Mei Wang Bo Shen Wei Zhu Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour Growth Stem Cells International |
| title | Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour Growth |
| title_full | Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour Growth |
| title_fullStr | Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour Growth |
| title_full_unstemmed | Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour Growth |
| title_short | Gastric Cancer Mesenchymal Stem Cells Inhibit NK Cell Function through mTOR Signalling to Promote Tumour Growth |
| title_sort | gastric cancer mesenchymal stem cells inhibit nk cell function through mtor signalling to promote tumour growth |
| url | http://dx.doi.org/10.1155/2021/9989790 |
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