Fluorouracil enhances the anti-pancreatic cancer effect of anti-PD-L1 antibodies via up-regulating the expression of PD-L1 in cancer cells
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View abstract on PubMed
Summary
This summary is machine-generated.Combining fluorouracil (5-FU) with anti-programmed cell death ligand 1 (PD-L1) antibodies enhances immune response in pancreatic cancer models. This combination increases PD-L1 expression and T-cell infiltration, improving anti-PD-L1 therapy effectiveness.
Area Of Science
- Immunology
- Oncology
- Pharmacology
Background
- Pancreatic cancer has poor prognosis due to late diagnosis and limited treatment options.
- Programmed cell death ligand 1 (PD-L1) expression is often low in pancreatic cancer, limiting immunotherapy efficacy.
- Fluorouracil (5-FU) can increase PD-L1 expression in pancreatic cancer cells.
Purpose Of The Study
- To investigate the synergistic effects of combining 5-FU with anti-PD-L1 antibodies in pancreatic cancer.
- To provide a rationale for the clinical use of PD-L1 inhibitors in pancreatic cancer treatment.
Main Methods
- A pancreatic cancer mouse model was established.
- Mice were treated with a combination of 5-FU and anti-mouse PD-L1 antibodies.
- Immunohistochemistry and Western blot assays were used to analyze PD-L1 expression, IFN-γ, CD8+ T cell infiltration, and signaling pathways (NF-κB, AKT).
Main Results
- The combination therapy significantly increased PD-L1 expression, IFN-γ levels, and CD8+ T cell infiltration in tumor tissues.
- Combined 5-FU and anti-PD-L1 treatment enhanced immune cytotoxicity in vivo.
- In vitro, 5-FU upregulated PD-L1 via the NF-κB and AKT pathways, an effect reversed by pathway inhibitors.
Conclusions
- 5-FU can sensitize pancreatic cancer to anti-PD-L1 therapy by upregulating PD-L1 expression through NF-κB and AKT pathways.
- Combination therapy demonstrates synergistic effects, enhancing anti-tumor immunity and providing a potential therapeutic strategy for pancreatic cancer.
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