A novel immune checkpoint siglec-15 antibody inhibits LUAD by modulating mφ polarization in TME
Background: Siglec-15 (S15) is a type-I transmembrane protein and is considered a new candidate of immune checkpoint inhibitor for cancer immunotherapy. Methods: In the present study, we first constructed and characterized a chimeric S15-specific monoclonal antibody (S15–4E6A). Then, the antitumor e...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661822002146 |
| _version_ | 1797366652100149248 |
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| author | Xuejun Xiao Yan Peng Zheyue Wang Louqian Zhang Tingting Yang Yangyang Sun Yufeng Chen Wenqing Zhang Xinxia Chang Wen Huang Shuning Tian Zhenqing Feng Nabi Xinhua Qi Tang Yuan Mao |
| author_facet | Xuejun Xiao Yan Peng Zheyue Wang Louqian Zhang Tingting Yang Yangyang Sun Yufeng Chen Wenqing Zhang Xinxia Chang Wen Huang Shuning Tian Zhenqing Feng Nabi Xinhua Qi Tang Yuan Mao |
| author_sort | Xuejun Xiao |
| collection | DOAJ |
| description | Background: Siglec-15 (S15) is a type-I transmembrane protein and is considered a new candidate of immune checkpoint inhibitor for cancer immunotherapy. Methods: In the present study, we first constructed and characterized a chimeric S15-specific monoclonal antibody (S15–4E6A). Then, the antitumor effectiveness and modulatory role of S15–4E6A in macrophages (mφs) were explored in vitro and in vivo. Finally, the underlying mechanism by which S15mAb inhibits LUAD was preliminarily explored. Results: The results demonstrated the successful construction of S15–4E6A, and S15–4E6A exerted an efficacious tumor-inhibitory effect on LUAD cells and xenografts. S15–4E6A could promote M1-mφ polarization while inhibiting M2-mφ polarization, both in vitro and in vivo. Conclusions: S15-based immunotherapy that functions by modulating mφ polarization may be a promising strategy for the treatment of S15-positive LUAD. |
| first_indexed | 2024-03-08T17:06:46Z |
| format | Article |
| id | doaj.art-4f986752e1014f1dbc9a7c9731e1849f |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-08T17:06:46Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-4f986752e1014f1dbc9a7c9731e1849f2024-01-04T04:37:47ZengElsevierPharmacological Research1096-11862022-07-01181106269A novel immune checkpoint siglec-15 antibody inhibits LUAD by modulating mφ polarization in TMEXuejun Xiao0Yan Peng1Zheyue Wang2Louqian Zhang3Tingting Yang4Yangyang Sun5Yufeng Chen6Wenqing Zhang7Xinxia Chang8Wen Huang9Shuning Tian10Zhenqing Feng11Nabi Xinhua12Qi Tang13Yuan Mao14Department of Pharmacology, Xinjiang Medical University, Urumqi, ChinaNHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China; Department of Pathology, Nanjing Medical University, Nanjing, ChinaNHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China; Department of Pathology, Nanjing Medical University, Nanjing, ChinaDepartment of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, ChinaNHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China; Department of Pathology, Nanjing Medical University, Nanjing, ChinaDepartment of Pathology, Changzhou No. 2 People's Hospital Affiliated with Nanjing Medical University, Changzhou, ChinaNHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China; Department of Pathology, Nanjing Medical University, Nanjing, ChinaNHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China; Department of Pathology, Nanjing Medical University, Nanjing, ChinaNHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China; Department of Pathology, Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaNHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, ChinaNHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China; Department of Pathology, Nanjing Medical University, Nanjing, ChinaDepartment of Pharmacology, Xinjiang Medical University, Urumqi, China; Corresponding author.NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China; Department of Pathology, Changzhou No. 2 People's Hospital Affiliated with Nanjing Medical University, Changzhou, China; Corresponding author at: NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, China.Department of Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Oncology, Geriatric Hospital of Nanjing Medical University, Nanjing, China; Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China; Corresponding author at: Department of Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China.Background: Siglec-15 (S15) is a type-I transmembrane protein and is considered a new candidate of immune checkpoint inhibitor for cancer immunotherapy. Methods: In the present study, we first constructed and characterized a chimeric S15-specific monoclonal antibody (S15–4E6A). Then, the antitumor effectiveness and modulatory role of S15–4E6A in macrophages (mφs) were explored in vitro and in vivo. Finally, the underlying mechanism by which S15mAb inhibits LUAD was preliminarily explored. Results: The results demonstrated the successful construction of S15–4E6A, and S15–4E6A exerted an efficacious tumor-inhibitory effect on LUAD cells and xenografts. S15–4E6A could promote M1-mφ polarization while inhibiting M2-mφ polarization, both in vitro and in vivo. Conclusions: S15-based immunotherapy that functions by modulating mφ polarization may be a promising strategy for the treatment of S15-positive LUAD.http://www.sciencedirect.com/science/article/pii/S1043661822002146Lung adenocarcinomasiglec-15Checkpoint inhibitorMacrophageTumor microenvironment |
| spellingShingle | Xuejun Xiao Yan Peng Zheyue Wang Louqian Zhang Tingting Yang Yangyang Sun Yufeng Chen Wenqing Zhang Xinxia Chang Wen Huang Shuning Tian Zhenqing Feng Nabi Xinhua Qi Tang Yuan Mao A novel immune checkpoint siglec-15 antibody inhibits LUAD by modulating mφ polarization in TME Pharmacological Research Lung adenocarcinoma siglec-15 Checkpoint inhibitor Macrophage Tumor microenvironment |
| title | A novel immune checkpoint siglec-15 antibody inhibits LUAD by modulating mφ polarization in TME |
| title_full | A novel immune checkpoint siglec-15 antibody inhibits LUAD by modulating mφ polarization in TME |
| title_fullStr | A novel immune checkpoint siglec-15 antibody inhibits LUAD by modulating mφ polarization in TME |
| title_full_unstemmed | A novel immune checkpoint siglec-15 antibody inhibits LUAD by modulating mφ polarization in TME |
| title_short | A novel immune checkpoint siglec-15 antibody inhibits LUAD by modulating mφ polarization in TME |
| title_sort | novel immune checkpoint siglec 15 antibody inhibits luad by modulating mφ polarization in tme |
| topic | Lung adenocarcinoma siglec-15 Checkpoint inhibitor Macrophage Tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S1043661822002146 |
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