PD-L1 knockout or ZG16 overexpression inhibits PDAC progression and modulates TAM polarization
CRISPR/Cas9-mediated genome editing has the potential to delete PD-L1 both on the cell surface and inside the cell, thereby inhibiting tumor growth and migration and overcoming immunosuppression. ZG16, with its lectin structure, can reduce PD-L1 expression on the cell surface. However, direct compar...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1510179/full |
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| author | Hui Meng Manman Nan Yizhen Li Yi Ding Xiaokun Fang Weiqian Ma Mingzhi Zhang |
| author_facet | Hui Meng Manman Nan Yizhen Li Yi Ding Xiaokun Fang Weiqian Ma Mingzhi Zhang |
| author_sort | Hui Meng |
| collection | DOAJ |
| description | CRISPR/Cas9-mediated genome editing has the potential to delete PD-L1 both on the cell surface and inside the cell, thereby inhibiting tumor growth and migration and overcoming immunosuppression. ZG16, with its lectin structure, can reduce PD-L1 expression on the cell surface. However, direct comparison of two approaches on PD-L1 expression in Pancreatic ductal adenocarcinoma (PDAC) cells has not yet been investigated. In this study, we established two Panc-1 cell line: one with PD-L1 knockout and another with ZG16 overexpression. Both methods promoted the polarization of tumor-associated macrophages (TAMs) to the M1 phenotype, as indicated by increased levels of the M1 marker CD11c+ in vitro and in vivo. Meanwhile, we observed a reduction in the M2 marker CD206+, upregulation of immune activation-related cytokines/chemokines, and a decrease in immunosuppressive cytokines and tumor angiogenesis factors. In summary, both PD-L1 knockout and ZG16 overexpression represent promising approaches for PDAC treatment. |
| format | Article |
| id | doaj-art-220aaaae5dc9485eaf3933e572352064 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-220aaaae5dc9485eaf3933e5723520642025-01-31T11:41:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15101791510179PD-L1 knockout or ZG16 overexpression inhibits PDAC progression and modulates TAM polarizationHui MengManman NanYizhen LiYi DingXiaokun FangWeiqian MaMingzhi ZhangCRISPR/Cas9-mediated genome editing has the potential to delete PD-L1 both on the cell surface and inside the cell, thereby inhibiting tumor growth and migration and overcoming immunosuppression. ZG16, with its lectin structure, can reduce PD-L1 expression on the cell surface. However, direct comparison of two approaches on PD-L1 expression in Pancreatic ductal adenocarcinoma (PDAC) cells has not yet been investigated. In this study, we established two Panc-1 cell line: one with PD-L1 knockout and another with ZG16 overexpression. Both methods promoted the polarization of tumor-associated macrophages (TAMs) to the M1 phenotype, as indicated by increased levels of the M1 marker CD11c+ in vitro and in vivo. Meanwhile, we observed a reduction in the M2 marker CD206+, upregulation of immune activation-related cytokines/chemokines, and a decrease in immunosuppressive cytokines and tumor angiogenesis factors. In summary, both PD-L1 knockout and ZG16 overexpression represent promising approaches for PDAC treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1510179/fullPD-L1 knockoutZG16 interventionCRISPR/Cas9PDAC progressionTAM polarization |
| spellingShingle | Hui Meng Manman Nan Yizhen Li Yi Ding Xiaokun Fang Weiqian Ma Mingzhi Zhang PD-L1 knockout or ZG16 overexpression inhibits PDAC progression and modulates TAM polarization Frontiers in Immunology PD-L1 knockout ZG16 intervention CRISPR/Cas9 PDAC progression TAM polarization |
| title | PD-L1 knockout or ZG16 overexpression inhibits PDAC progression and modulates TAM polarization |
| title_full | PD-L1 knockout or ZG16 overexpression inhibits PDAC progression and modulates TAM polarization |
| title_fullStr | PD-L1 knockout or ZG16 overexpression inhibits PDAC progression and modulates TAM polarization |
| title_full_unstemmed | PD-L1 knockout or ZG16 overexpression inhibits PDAC progression and modulates TAM polarization |
| title_short | PD-L1 knockout or ZG16 overexpression inhibits PDAC progression and modulates TAM polarization |
| title_sort | pd l1 knockout or zg16 overexpression inhibits pdac progression and modulates tam polarization |
| topic | PD-L1 knockout ZG16 intervention CRISPR/Cas9 PDAC progression TAM polarization |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1510179/full |
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