Mediating immunosuppressive functions: a new perspective on the complex immunological properties of SEMA4D in the tumor microenvironment
Semaphorin 4D (SEMA4D) is considered a new antitumor target closely related to immune cells. However, understanding the role of SEMA4D in the tumor microenvironment (TME) is limited. In this study, we explored the expression and immune cell infiltration patterns of SEMA4D using multiple bioinformati...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1171926/full |
| _version_ | 1797822021426479104 |
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| author | Shujie Zeng Shujie Zeng Zihao Zhang Zihao Zhang Chunshui Ye Chunshui Ye Jinshen Wang Jinshen Wang Jinshen Wang Changqing Jing Changqing Jing Leping Li Leping Li Leping Li Leping Li |
| author_facet | Shujie Zeng Shujie Zeng Zihao Zhang Zihao Zhang Chunshui Ye Chunshui Ye Jinshen Wang Jinshen Wang Jinshen Wang Changqing Jing Changqing Jing Leping Li Leping Li Leping Li Leping Li |
| author_sort | Shujie Zeng |
| collection | DOAJ |
| description | Semaphorin 4D (SEMA4D) is considered a new antitumor target closely related to immune cells. However, understanding the role of SEMA4D in the tumor microenvironment (TME) is limited. In this study, we explored the expression and immune cell infiltration patterns of SEMA4D using multiple bioinformatics datasets and analyzed the relationship between SEMA4D expression with immune checkpoints, tumor mutational load (TMB), microsatellite instability (MSI) and immune function. We detected that SEMA4D is overexpressed in many tumors types, widely enriched in immune cells, and closely associated with TILs, MSI, TMB, as well as T-cell exhaustion-associated immune checkpoints, and thus can broadly affect the immune microenvironment. We further verified the overexpression of SEMA4D in tumor and its distribution in TME by immunohistochemistry, RT-qPCR and flow cytometry, and confirmed that decreased expression of SEMA4D can lead to recovery of T cell exhaustion. In conlusion, this study provides a more comprehensive perspective of SEMA4D regulation of tumor immunity, which provide a new option for cancer immunotherapy. |
| first_indexed | 2024-03-13T10:01:41Z |
| format | Article |
| id | doaj.art-e12a4f96a85a40c8b713db05c1cc53e3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-13T10:01:41Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e12a4f96a85a40c8b713db05c1cc53e32023-05-23T05:26:40ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.11719261171926Mediating immunosuppressive functions: a new perspective on the complex immunological properties of SEMA4D in the tumor microenvironmentShujie Zeng0Shujie Zeng1Zihao Zhang2Zihao Zhang3Chunshui Ye4Chunshui Ye5Jinshen Wang6Jinshen Wang7Jinshen Wang8Changqing Jing9Changqing Jing10Leping Li11Leping Li12Leping Li13Leping Li14Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterological Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterological Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterological Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterological Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaKey Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital, Jinan, Shandong, ChinaDepartment of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterological Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterological Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaKey Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital, Jinan, Shandong, ChinaMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, ChinaSemaphorin 4D (SEMA4D) is considered a new antitumor target closely related to immune cells. However, understanding the role of SEMA4D in the tumor microenvironment (TME) is limited. In this study, we explored the expression and immune cell infiltration patterns of SEMA4D using multiple bioinformatics datasets and analyzed the relationship between SEMA4D expression with immune checkpoints, tumor mutational load (TMB), microsatellite instability (MSI) and immune function. We detected that SEMA4D is overexpressed in many tumors types, widely enriched in immune cells, and closely associated with TILs, MSI, TMB, as well as T-cell exhaustion-associated immune checkpoints, and thus can broadly affect the immune microenvironment. We further verified the overexpression of SEMA4D in tumor and its distribution in TME by immunohistochemistry, RT-qPCR and flow cytometry, and confirmed that decreased expression of SEMA4D can lead to recovery of T cell exhaustion. In conlusion, this study provides a more comprehensive perspective of SEMA4D regulation of tumor immunity, which provide a new option for cancer immunotherapy.https://www.frontiersin.org/articles/10.3389/fonc.2023.1171926/fullSEMA4Dpancancertumor microenvironmentimmune infiltrationexhaustion of CD8+ T cell |
| spellingShingle | Shujie Zeng Shujie Zeng Zihao Zhang Zihao Zhang Chunshui Ye Chunshui Ye Jinshen Wang Jinshen Wang Jinshen Wang Changqing Jing Changqing Jing Leping Li Leping Li Leping Li Leping Li Mediating immunosuppressive functions: a new perspective on the complex immunological properties of SEMA4D in the tumor microenvironment Frontiers in Oncology SEMA4D pancancer tumor microenvironment immune infiltration exhaustion of CD8+ T cell |
| title | Mediating immunosuppressive functions: a new perspective on the complex immunological properties of SEMA4D in the tumor microenvironment |
| title_full | Mediating immunosuppressive functions: a new perspective on the complex immunological properties of SEMA4D in the tumor microenvironment |
| title_fullStr | Mediating immunosuppressive functions: a new perspective on the complex immunological properties of SEMA4D in the tumor microenvironment |
| title_full_unstemmed | Mediating immunosuppressive functions: a new perspective on the complex immunological properties of SEMA4D in the tumor microenvironment |
| title_short | Mediating immunosuppressive functions: a new perspective on the complex immunological properties of SEMA4D in the tumor microenvironment |
| title_sort | mediating immunosuppressive functions a new perspective on the complex immunological properties of sema4d in the tumor microenvironment |
| topic | SEMA4D pancancer tumor microenvironment immune infiltration exhaustion of CD8+ T cell |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1171926/full |
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