PD-L1 monoclonal antibody alleviated MI injury of left ventricular function via modulating CD47/SHP2/SIRPα/SYK/FcγR signalings in tumor associated macrophages
Abstract To investigate how PD-L1 monoclonal antibodies (mAbs) affect the left ventricular function in mice with myocardial infarction (MI) and through what mechanisms they exert their effects. In vivo experiments were conducted using 27 female BALB/c mice, which were divided equally into 3 groups....
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-85065-w |
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| author | Deyou Kong Yongzhen Chen Yajuan Yin Zhikun Liu Fang Yang Xiaohong Li Dongxing Shen Jun Zhang |
| author_facet | Deyou Kong Yongzhen Chen Yajuan Yin Zhikun Liu Fang Yang Xiaohong Li Dongxing Shen Jun Zhang |
| author_sort | Deyou Kong |
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| description | Abstract To investigate how PD-L1 monoclonal antibodies (mAbs) affect the left ventricular function in mice with myocardial infarction (MI) and through what mechanisms they exert their effects. In vivo experiments were conducted using 27 female BALB/c mice, which were divided equally into 3 groups. Cardiac function was assessed by ultrasound. Heart tissue and breast cancer tumor samples were isolated, and the content of cGAMP was measured using LC-MS/MS. The extent of myocardial infarction was evaluated by Masson staining. In vitro experiments involved dividing macrophages, treated with different inducers, into 8 groups. Protein expression levels in each group were analyzed by Western blotting, and the macrophages were transplanted into experimental mice for observation. In the in vivo experiments, ultrasound examination showed that PD-L1 mAb improved cardiac function in mice with breast cancer and MI. Both cGAMP content measurement and Masson staining results indicated that PD-L1 mAb had a therapeutic effect on mice with breast cancer and MI, improving the infarct condition and slowing tumor progression. In vitro Western blotting analysis revealed that PD-L1 mAb can modulate the CD47/SHP2/SIRPα/SYK/FcγR signaling pathway, thereby affecting breast cancer. Treatment with a STING inhibitor significantly reduced the cGAMP effect, leading to improved left ventricular function in mice with MI. PD-L1 monoclonal antibodies improve left ventricular function in mice with myocardial infarction by modulating the CD47/SHP2/SIRPα/SYK/FcγR signaling pathway in tumor-associated macrophages and inhibiting the expression of cGAMP. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-2ced5e48b3f04bdc850bd662bdc3759a2025-01-19T12:23:40ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-024-85065-wPD-L1 monoclonal antibody alleviated MI injury of left ventricular function via modulating CD47/SHP2/SIRPα/SYK/FcγR signalings in tumor associated macrophagesDeyou Kong0Yongzhen Chen1Yajuan Yin2Zhikun Liu3Fang Yang4Xiaohong Li5Dongxing Shen6Jun Zhang7Department of Radiotherapy, The Fourth Hospital of Hebei Medical UniversityDepartment of Function, The Fourth Hospital of Hebei Medical UniversityDepartment of Cardiology, The First Hospital of Hebei Medical UniversityDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical UniversityDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical UniversityDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical UniversityDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical UniversityDepartment of Radiotherapy, The Fourth Hospital of Hebei Medical UniversityAbstract To investigate how PD-L1 monoclonal antibodies (mAbs) affect the left ventricular function in mice with myocardial infarction (MI) and through what mechanisms they exert their effects. In vivo experiments were conducted using 27 female BALB/c mice, which were divided equally into 3 groups. Cardiac function was assessed by ultrasound. Heart tissue and breast cancer tumor samples were isolated, and the content of cGAMP was measured using LC-MS/MS. The extent of myocardial infarction was evaluated by Masson staining. In vitro experiments involved dividing macrophages, treated with different inducers, into 8 groups. Protein expression levels in each group were analyzed by Western blotting, and the macrophages were transplanted into experimental mice for observation. In the in vivo experiments, ultrasound examination showed that PD-L1 mAb improved cardiac function in mice with breast cancer and MI. Both cGAMP content measurement and Masson staining results indicated that PD-L1 mAb had a therapeutic effect on mice with breast cancer and MI, improving the infarct condition and slowing tumor progression. In vitro Western blotting analysis revealed that PD-L1 mAb can modulate the CD47/SHP2/SIRPα/SYK/FcγR signaling pathway, thereby affecting breast cancer. Treatment with a STING inhibitor significantly reduced the cGAMP effect, leading to improved left ventricular function in mice with MI. PD-L1 monoclonal antibodies improve left ventricular function in mice with myocardial infarction by modulating the CD47/SHP2/SIRPα/SYK/FcγR signaling pathway in tumor-associated macrophages and inhibiting the expression of cGAMP.https://doi.org/10.1038/s41598-024-85065-wPD-L1CD47/SHP2/SIRPα/SYK/FcγR signaling pathwaycGAMPBreast cancerMyocardial infarction |
| spellingShingle | Deyou Kong Yongzhen Chen Yajuan Yin Zhikun Liu Fang Yang Xiaohong Li Dongxing Shen Jun Zhang PD-L1 monoclonal antibody alleviated MI injury of left ventricular function via modulating CD47/SHP2/SIRPα/SYK/FcγR signalings in tumor associated macrophages Scientific Reports PD-L1 CD47/SHP2/SIRPα/SYK/FcγR signaling pathway cGAMP Breast cancer Myocardial infarction |
| title | PD-L1 monoclonal antibody alleviated MI injury of left ventricular function via modulating CD47/SHP2/SIRPα/SYK/FcγR signalings in tumor associated macrophages |
| title_full | PD-L1 monoclonal antibody alleviated MI injury of left ventricular function via modulating CD47/SHP2/SIRPα/SYK/FcγR signalings in tumor associated macrophages |
| title_fullStr | PD-L1 monoclonal antibody alleviated MI injury of left ventricular function via modulating CD47/SHP2/SIRPα/SYK/FcγR signalings in tumor associated macrophages |
| title_full_unstemmed | PD-L1 monoclonal antibody alleviated MI injury of left ventricular function via modulating CD47/SHP2/SIRPα/SYK/FcγR signalings in tumor associated macrophages |
| title_short | PD-L1 monoclonal antibody alleviated MI injury of left ventricular function via modulating CD47/SHP2/SIRPα/SYK/FcγR signalings in tumor associated macrophages |
| title_sort | pd l1 monoclonal antibody alleviated mi injury of left ventricular function via modulating cd47 shp2 sirpα syk fcγr signalings in tumor associated macrophages |
| topic | PD-L1 CD47/SHP2/SIRPα/SYK/FcγR signaling pathway cGAMP Breast cancer Myocardial infarction |
| url | https://doi.org/10.1038/s41598-024-85065-w |
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