Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 11, 2024 1 month, 2 weeks, 2 days, 2 hours, 38 minutes ago
Cancer News: Researchers from Washington University School of Medicine in St. Louis and Dana-Farber Cancer Institute in Boston have discovered crucial insights into how gastric cancer behaves and responds to treatment. Their study covered in this
Cancer News report, explores the intricate patterns of PD-L1 expression in gastric cancer, providing hope for more effective treatments in the future.
PD-L1 expression in gastric cancer cells and tumor tissues. (A) Western blot of whole NCIN87 cell lysates after cells’ incubation with INF-γ (0.5 ng IFN-γ per 1 million of NCIN87 cancer cells) during 0, 8, 24, 48, 72, 96 (h). The quantification of PD-L1 protein levels was normalized to β-actin at each time point in duplicate. (B) PD-L1 immunohistochemistry in gastric PDXs and NCIN87 gastric tumor tissues. Scale bar, 1 mm and 50 µm. (C) Representative whole-body PET/CT images acquired 48 h post tail vein injection of [89Zr]Zr-DFO-avelumab in mice bearing NCIN87 xenografts.
Understanding PD-L1 and Its Role in Cancer
PD-L1, or programmed death-ligand 1, is a protein that plays a significant role in cancer by helping tumors evade the immune system. When PD-L1 on cancer cells binds to the PD-1 receptor on T-cells, it suppresses the immune response, allowing the cancer to grow unchecked. Immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 have revolutionized cancer treatment, but their effectiveness in gastric cancer has been inconsistent.
A Closer Look at Gastric Cancer
Gastric cancer, also known as stomach cancer, has been particularly challenging to treat with ICIs. The expression of PD-L1 in gastric tumors is highly variable and can change over time. This variability makes it difficult to predict which patients will respond well to PD-1/PD-L1 blockade therapies.
The Study's Objectives
The research team aimed to investigate the dynamics of PD-L1 expression in gastric cancer cells and tissues. They also explored how two FDA-approved anti-PD-L1 antibodies, avelumab and atezolizumab, bind to PD-L1 in these cells. Additionally, they examined the impact of PD-L1 glycosylation (a type of molecular modification) on antibody binding.
Methodology
The study involved several sophisticated techniques:
-Cell Culture and Treatments: Gastric cancer cells (NCIN87) were cultured and treated with interferon-gamma (IFN-γ) to induce PD-L1 expression.
-PET Imaging: Positron emission tomography (PET) imaging was used to visualize the uptake of radiolabeled antibodies in tumor cells.
-Western Blot Analysis: This technique was used to analyze PD-L1 expression and glycosylation status in the cells.
-Binding Assays: Comparative studies were conducted to
see how well avelumab and atezolizumab bound to PD-L1 on cancer cells.
Key Findings
The researchers uncovered several critical findings:
-Dynamic and Heterogeneous Expression: PD-L1 expression in gastric cancer cells changes over time and varies within different areas of the tumor. This heterogeneity was clearly visible in PET imaging.
-Superior Binding of Avelumab: Avelumab showed a higher binding affinity to PD-L1 in gastric cancer cells compared to atezolizumab. This was confirmed through in vivo PET imaging and ex vivo biodistribution studies.
-Impact of Glycosylation: PD-L1 glycosylation significantly affects antibody binding. Removing glycosylation enhanced the binding of avelumab to PD-L1, making it more effective in targeting the cancer cells.
Implications for Treatment
These findings have important implications for cancer treatment. The dynamic nature of PD-L1 expression and its modification through glycosylation must be considered when developing and using PD-L1 targeting therapies. The superior binding of avelumab suggests that it might be a more effective option for imaging and potentially treating gastric cancer compared to atezolizumab.
Future Directions
The study highlights the need for further research to refine PD-L1-targeting strategies. Understanding the complexities of PD-L1 expression and its interactions with therapeutic antibodies can lead to more personalized and effective treatment approaches for gastric cancer patients.
A Step Forward
This research represents a significant step forward in the fight against gastric cancer. By uncovering the dynamic and heterogeneous nature of PD-L1 expression, scientists are paving the way for more accurate and effective treatments. The promise of avelumab as a superior antibody for targeting PD-L1 brings hope for better outcomes in gastric cancer therapy.
In conclusion, this study emphasizes the importance of ongoing research and innovation in cancer treatment. By continuing to explore and understand the complexities of tumor biology, we can develop more targeted and effective therapies, ultimately improving the lives of cancer patients.
For those interested in delving deeper into this research, the full study can be accessed in the peer reviewed journal: Frontiers in Immunology, under the title "PD-L1 has a heterogeneous and dynamic expression in gastric cancer with implications for immunoPET."
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1405485/full
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