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PD-L1 knockout or ZG16 overexpression inhibits PDAC progression and modulates TAM polarization
Hui Meng1, Manman Nan1, Yizhen Li1
1Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Frontiers in Immunology
|February 17, 2025
Summary
CRISPR/Cas9 gene editing and ZG16 protein can reduce PD-L1 expression in pancreatic cancer cells. Both approaches enhance anti-tumor immunity by reprogramming macrophages and reducing immunosuppression, offering promising therapeutic strategies for pancreatic ductal adenocarcinoma (PDAC).
Area of Science:
- Immunology
- Genetics
- Oncology
Background:
- Programmed death-ligand 1 (PD-L1) is a key immune checkpoint in cancer.
- PD-L1 expression on tumor cells contributes to immune evasion.
- Targeting PD-L1 is a validated strategy in cancer immunotherapy.
Purpose of the Study:
- To compare CRISPR/Cas9-mediated PD-L1 knockout with ZG16 overexpression in pancreatic ductal adenocarcinoma (PDAC) cells.
- To investigate the effects of these approaches on tumor-associated macrophage (TAM) polarization and the tumor microenvironment.
- To evaluate their potential as therapeutic strategies for PDAC.
Main Methods:
- Established Panc-1 cell lines with PD-L1 knockout using CRISPR/Cas9.
- Established Panc-1 cell lines with ZG16 overexpression.
- Assessed TAM polarization (M1/M2 phenotype markers), cytokine/chemokine profiles, and tumor angiogenesis factors in vitro and in vivo.
Main Results:
- Both PD-L1 knockout and ZG16 overexpression promoted M1 TAM polarization (increased CD11c+) and reduced M2 TAM polarization (decreased CD206+).
- Upregulation of immune activation-related cytokines/chemokines and downregulation of immunosuppressive cytokines were observed.
- A decrease in tumor angiogenesis factors was noted in both treatment groups.
Conclusions:
- Both PD-L1 knockout and ZG16 overexpression are effective in modulating the tumor immune microenvironment in PDAC.
- These strategies show potential for overcoming immunosuppression and inhibiting tumor progression in PDAC.
- Further investigation into these approaches for PDAC treatment is warranted.
