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Published on: February 8, 2018
Evaluation of Neutrophil Activation Biomarkers in Response to Programmed Cell Death Protein-1 (PD-1) and Toll-like
Sara Youssry1, Amina Hussein1, Nadia Abd El Moneim2
1Department of Immunology and Allergy, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Background And Objective:
Activation of neutrophils has proven to be useful in different models of cancer therapy. However, more comprehensive studies are required to further characterize these potential targets. Thus, we aimed to evaluate the effects of programmed cell death protein-1 (PD-1) and toll-like receptor 9 (TLR-9) inhibition on markers of neutrophil activation in different breast cancer subtypes.
Methods:
Neutrophils were cultured and treated with PD-1 and TLR-9 inhibitors after being isolated from 43 triple negative breast cancer (TNBC), 31 non-TNBC patients and 30 healthy females. Enzyme linked immunosorbent assay (ELISA) was then used to detect neutrophil elastase (NE) and myeloperoxidase (MPO) in culture supernatants.
Results:
The results revealed that increased NE and MPO were significantly associated with advanced clinical stage and vascular invasion, respectively. In addition, treatment with either anti-PD-1 or anti-TLR-9 was associated with a significant decrease in NE and MPO levels of both TNBC and non-TNBC samples compared to untreated samples. Moreover, the ameliorative effect of both treatments was observed to be more obvious on MPO levels compared to NE levels in breast cancer subtypes.
Conclusion:
These results may highlight the possible therapeutic role of PD-1 and TLR-9 inhibitors in modulating neutrophil activation markers (NE and MPO) in breast cancer subtypes.
Insights
Programmed cell death protein-1 (PD-1) and toll-like receptor 9 (TLR-9) inhibition reduced neutrophil activation markers, neutrophil elastase (NE) and myeloperoxidase (MPO), in triple negative breast cancer (TNBC) and non-TNBC subtypes. These findings suggest a potential therapeutic role for these inhibitors.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Neutrophil activation is a promising avenue for cancer therapy.
- Further characterization of neutrophil activation targets is needed.
- Programmed cell death protein-1 (PD-1) and toll-like receptor 9 (TLR-9) are potential targets.
Purpose of the Study:
- To evaluate the effects of PD-1 and TLR-9 inhibition on neutrophil activation markers.
- To investigate these effects in different breast cancer subtypes, including triple-negative breast cancer (TNBC).
Main Methods:
- Neutrophils were isolated from TNBC patients, non-TNBC patients, and healthy females.
- Neutrophils were treated with PD-1 and TLR-9 inhibitors.
- Enzyme-linked immunosorbent assay (ELISA) measured neutrophil elastase (NE) and myeloperoxidase (MPO) levels.
Main Results:
- Increased NE and MPO levels correlated with advanced clinical stage and vascular invasion, respectively.
- Both anti-PD-1 and anti-TLR-9 treatments significantly decreased NE and MPO levels in TNBC and non-TNBC samples.
- The inhibitory effect was more pronounced on MPO levels than NE levels.
Conclusions:
- PD-1 and TLR-9 inhibitors show potential in modulating neutrophil activation markers in breast cancer.
- These findings suggest a possible therapeutic strategy for breast cancer subtypes.
