Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma
Background Siglec-E is an immune checkpoint inhibitory molecule. Expression of Siglec-E on the immune cells has been shown to promote tumor regression. This study aimed to develop an adenovirus (Ad) vaccine targeting Siglec-E and carbonic anhydrase IX (CAIX) (Ad-Siglec-E/CAIX) and to evaluate its po...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2025-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/1/e010521.full |
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| author | Yuchen Zhang Junnian Zheng Li Sun Guangya Zhao Yingxiang Shao Bowen Lu Jiage Ding Yanyan Zheng Renjin Chen Dafei Chai Jiawei Wang Zichun Zhang Xiaohui Xie |
| author_facet | Yuchen Zhang Junnian Zheng Li Sun Guangya Zhao Yingxiang Shao Bowen Lu Jiage Ding Yanyan Zheng Renjin Chen Dafei Chai Jiawei Wang Zichun Zhang Xiaohui Xie |
| author_sort | Yuchen Zhang |
| collection | DOAJ |
| description | Background Siglec-E is an immune checkpoint inhibitory molecule. Expression of Siglec-E on the immune cells has been shown to promote tumor regression. This study aimed to develop an adenovirus (Ad) vaccine targeting Siglec-E and carbonic anhydrase IX (CAIX) (Ad-Siglec-E/CAIX) and to evaluate its potential antitumor effects in several preclinical renal cancer models.Methods Ad vaccines encoding Siglec-E or CAIX were developed and evaluated for their therapeutic potential in mouse subcutaneous, lung metastatic, and orthotopic tumor models. The expression of Ad-Siglec-E/CAIX was confirmed via PCR and flow cytometry. Immune responses induced by Ad-Siglec-E/CAIX were assessed in vitro and in vivo using flow cytometry, immunohistochemistry, ELISA, histological analysis, cell proliferation, enzyme-linked immunosorbent spot, cytotoxic T lymphocytes (CTL) killing, and cell depletion assays.Results Ad-Siglec-E/CAIX vaccine induced the increase of tumor-infiltrated immune cells, and significantly suppressed the subcutaneous tumor growth of renal carcinoma. Immunization with Ad-Siglec-E/CAIX promoted the induction and maturation of CD11c+ dendritic cells and their subsets, which in turn enhanced tumor-specific CD8+ T cell immune responses, as evidenced by increased CD8+ T cell proliferation and CTL activity. Importantly, the deletion of CD8+ T cells in vivo abolished the antitumor effect of the Ad-Siglec-E/CAIX vaccine, highlighting the essential role of functional CD8+ T cell responses. The potent therapeutic efficacy of the Ad-Siglec-E/CAIX vaccine was also observed in lung metastasis and orthotopic tumor models through tumor-specific CD8+ T cell immune responses.Conclusions Our results indicate that targeting Siglec-E enhances the therapeutic efficacy of Ad-CAIX against renal carcinoma, providing a promising therapeutic option for solid tumors. |
| format | Article |
| id | doaj-art-a6285c4a813d45ce9201fd2d54d2b488 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-a6285c4a813d45ce9201fd2d54d2b4882025-01-07T18:05:11ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-01-0113110.1136/jitc-2024-010521Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinomaYuchen Zhang0Junnian Zheng1Li Sun2Guangya Zhao3Yingxiang Shao4Bowen Lu5Jiage Ding6Yanyan Zheng7Renjin Chen8Dafei Chai9Jiawei Wang10Zichun Zhang11Xiaohui Xie12College of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaCenter of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, ChinaDepartment of Oncology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaDepartment of Oncology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaCollege of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaCancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, ChinaDepartment of Oncology, Ninghe District Hospital of Tianjin, Tianjin, ChinaDepartment of Urology, The Yancheng Clinical College of Xuzhou Medical University, Yancheng City No 1 People’s Hospital, Yancheng, Jiangsu, ChinaDepartment of Medicine, Baylor College of Medicine, Houston, Texas, USABackground Siglec-E is an immune checkpoint inhibitory molecule. Expression of Siglec-E on the immune cells has been shown to promote tumor regression. This study aimed to develop an adenovirus (Ad) vaccine targeting Siglec-E and carbonic anhydrase IX (CAIX) (Ad-Siglec-E/CAIX) and to evaluate its potential antitumor effects in several preclinical renal cancer models.Methods Ad vaccines encoding Siglec-E or CAIX were developed and evaluated for their therapeutic potential in mouse subcutaneous, lung metastatic, and orthotopic tumor models. The expression of Ad-Siglec-E/CAIX was confirmed via PCR and flow cytometry. Immune responses induced by Ad-Siglec-E/CAIX were assessed in vitro and in vivo using flow cytometry, immunohistochemistry, ELISA, histological analysis, cell proliferation, enzyme-linked immunosorbent spot, cytotoxic T lymphocytes (CTL) killing, and cell depletion assays.Results Ad-Siglec-E/CAIX vaccine induced the increase of tumor-infiltrated immune cells, and significantly suppressed the subcutaneous tumor growth of renal carcinoma. Immunization with Ad-Siglec-E/CAIX promoted the induction and maturation of CD11c+ dendritic cells and their subsets, which in turn enhanced tumor-specific CD8+ T cell immune responses, as evidenced by increased CD8+ T cell proliferation and CTL activity. Importantly, the deletion of CD8+ T cells in vivo abolished the antitumor effect of the Ad-Siglec-E/CAIX vaccine, highlighting the essential role of functional CD8+ T cell responses. The potent therapeutic efficacy of the Ad-Siglec-E/CAIX vaccine was also observed in lung metastasis and orthotopic tumor models through tumor-specific CD8+ T cell immune responses.Conclusions Our results indicate that targeting Siglec-E enhances the therapeutic efficacy of Ad-CAIX against renal carcinoma, providing a promising therapeutic option for solid tumors.https://jitc.bmj.com/content/13/1/e010521.full |
| spellingShingle | Yuchen Zhang Junnian Zheng Li Sun Guangya Zhao Yingxiang Shao Bowen Lu Jiage Ding Yanyan Zheng Renjin Chen Dafei Chai Jiawei Wang Zichun Zhang Xiaohui Xie Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma Journal for ImmunoTherapy of Cancer |
| title | Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma |
| title_full | Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma |
| title_fullStr | Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma |
| title_full_unstemmed | Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma |
| title_short | Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma |
| title_sort | targeting siglec e facilitates tumor vaccine induced antitumor immunity in renal carcinoma |
| url | https://jitc.bmj.com/content/13/1/e010521.full |
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