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Increased apoptosis and elevated Fas expression in circulating natural killer cells in gastric cancer patients
Hiroaki Saito1, Seigo Takaya, Tomohiro Osaki
1Division of Surgical Oncology, Department of Surgery, Tottori University School of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan, sai10@med.tottori-u.ac.jp.
Background:
Immune cells undergo extensive apoptosis in patients with cancer, which may be related to immune evasion by cancerous cells. The present study was designed to investigate the relationship between natural killer (NK) cell apoptosis and Fas expression in gastric cancer patients.
Methods:
NK cell apoptosis and Fas expression were evaluated by multicolor flow cytometry. Soluble Fas ligand (sFasL) was quantitated by enzyme-linked immunosorbent assay.
Results:
The frequency of apoptotic NK cells in gastric cancer patients was significantly higher than in normal controls (p = 0.0016). Moreover, their frequency was related to the progression of gastric cancer. Fas-positive NK cells were significantly more common in gastric cancer patients compared with normal controls (p = 0.034). Furthermore, Fas expression was closely related to the frequency of NK cell apoptosis (r = 0.6, p < 0.0001). The frequency of tumor-infiltrating NK cell apoptosis was significantly higher than that of circulating NK cell apoptosis (p = 0.035). Furthermore, Fas-positive NK cells in gastric cancer tissues occurred significantly more often than in peripheral blood (p = 0.029). FasL concentration in gastric cancer patients was lower than that in normal controls, and the difference tended to be significant (p = 0.057). Apoptotic circulating NK cells significantly decreased after surgery compared to before surgery (p = 0.023). Furthermore, Fas expression on circulating NK cells also significantly decreased after surgery compared with before surgery (p = 0.021).
Conclusions:
Upregulation of Fas expression on NK cells is related to increased apoptosis of circulating NK cells in gastric cancer patients.
Insights
Natural killer (NK) cell apoptosis is increased in gastric cancer patients, linked to higher Fas expression. This apoptosis, particularly in circulating NK cells, decreases after surgery, suggesting Fas upregulation contributes to immune evasion in gastric cancer.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Cancer cells can evade immune detection through mechanisms like inducing apoptosis in immune cells.
- Natural killer (NK) cells play a crucial role in anti-tumor immunity.
- Understanding NK cell apoptosis in gastric cancer is vital for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the relationship between NK cell apoptosis and Fas expression in gastric cancer patients.
- To compare NK cell apoptosis and Fas expression in tumor tissues versus peripheral blood.
- To assess the impact of surgery on NK cell apoptosis and Fas expression.
Main Methods:
- Multicolor flow cytometry was used to evaluate NK cell apoptosis and Fas expression.
- Enzyme-linked immunosorbent assay (ELISA) quantified soluble Fas ligand (sFasL) levels.
- Comparisons were made between gastric cancer patients and healthy controls, and pre- vs. post-surgery.
Main Results:
- Gastric cancer patients exhibited significantly higher frequencies of apoptotic NK cells and Fas-positive NK cells compared to controls.
- Fas expression strongly correlated with NK cell apoptosis.
- Tumor-infiltrating NK cells showed higher apoptosis rates than circulating NK cells.
- Apoptotic circulating NK cells and Fas expression decreased significantly after surgical tumor removal.
Conclusions:
- Increased Fas expression on NK cells is associated with elevated apoptosis of circulating NK cells in gastric cancer.
- These findings suggest Fas-mediated apoptosis contributes to immune evasion in gastric cancer.
- NK cell apoptosis and Fas expression are potential biomarkers for gastric cancer progression and treatment response.
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