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Peripheral blood T lymphocytes are downregulated by the PD-1/PD-L1 axis in advanced gastric cancer
Witold Zgodzinski1, Ewelina Grywalska2, Krzysztof Zinkiewicz1
12 Department of General, Gastrointestinal Surgery and Surgical Oncology of the Alimentary Tract, Medical University of Lublin, Lublin, Poland.
Introduction:
Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) function as an immune checkpoint pathway that can be exploited by tumor cells to evade immuno-surveillance. The precise role of PD-1/PD-L1 inhibition of the immune response in GC is unknown. The study investigated PD-1 and PD-L1 expression on peripheral T-cells and its potential association with clinicopathological features in gastric cancer (GC) patients.
Material And Methods:
PD-1/PD-L1 expression on CD4(+) and CD8(+) T-cells from peripheral blood of 40 patients primarily diagnosed with advanced GC was evaluated by multicolor flow cytometry.
Results:
The frequency of CD4(+)PD-1(+) and CD8(+)PD-1(+) cells in GC patients was higher than in the control group (p < 0.0001 and p < 0.01, respectively). Expression of PD-1 on CD8(+) cells in GC was higher than in the control group (p < 0.0001). The frequency of CD4(+)PD-L1(+) and CD8(+)PD-L1(+) cells was higher than in the control group (p < 0.0001). Expression of PD-L1 on CD4(+) and CD8(+) cells in GC was higher than in the control group (p < 0.0001). A higher frequency of CD4(+)PD-1(+) cells was found in diffuse-type compared to intestinal tumors (p < 0.029). A higher frequency of CD8(+)PD-1(+) cells was found in patients with poorly differentiated compared to well/moderately differentiated tumors (p < 0.019).
Conclusions:
Downregulation of peripheral blood CD4(+) and CD8(+) lymphocytes can be associated with PD-1/PD-L1 expression. This can lead to attenuation of the general immune response in GC.
Insights
Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) expression is elevated on T-cells in gastric cancer (GC) patients, suggesting immune evasion. This immune checkpoint upregulation may contribute to a weakened immune response in GC.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) are key immune checkpoint proteins.
- Tumor cells exploit the PD-1/PD-L1 pathway to evade immune surveillance.
- The specific role of PD-1/PD-L1 in gastric cancer (GC) immunity is not fully understood.
Purpose of the Study:
- To investigate PD-1 and PD-L1 expression on peripheral T-cells in gastric cancer patients.
- To determine the association between PD-1/PD-L1 expression and clinicopathological features in GC.
Main Methods:
- Multicolor flow cytometry was used to evaluate PD-1 and PD-L1 expression.
- Peripheral blood T-cells (CD4(+) and CD8(+)) from 40 advanced GC patients and controls were analyzed.
Main Results:
- GC patients showed significantly higher frequencies of CD4(+)PD-1(+), CD8(+)PD-1(+), CD4(+)PD-L1(+), and CD8(+)PD-L1(+) cells compared to controls.
- PD-1 expression on CD8(+) T-cells was notably higher in GC patients.
- Elevated CD4(+)PD-1(+) cells correlated with diffuse-type GC, while increased CD8(+)PD-1(+) cells were linked to poorly differentiated tumors.
Conclusions:
- Upregulation of PD-1 and PD-L1 on peripheral T-cells is associated with gastric cancer.
- This immune checkpoint expression may lead to the downregulation of T-cell function.
- The findings suggest an attenuated immune response in GC patients due to PD-1/PD-L1 pathway activation.
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