Activation of PGE2/EP2 and PGE2/EP4 signaling pathways positively regulate the level of PD‑1 in infiltrating CD8+ T cells in patients with lung cancer
- Jinhong Wang
- Li Zhang
- Dong Kang
- Deguang Yang
- Ying Tang
Published online on: October 26, 2017
The present study aimed to identify the level of programmed death‑1 (PD‑1) expression in infiltrating cluster of differentiation (CD)4+ and CD8+ T cells isolated from lung cancer tissues, and investigated whether the level of PD‑1 expression may be directly regulated by lung cancer cells via prostaglandin E2 (PGE2)‑associated signaling pathways in patients with lung cancer. A total of 75 patients with lung cancer were enrolled in the present study. The percentage of infiltrating CD4+ and CD8+ T cells was determined by flow cytometry. ELISA was performed to evaluate the concentration of PGE2 in lung cancer tissue homogenate. The correlation between PGE2 and PD‑1 expression levels in CD8+ T cells was assessed by Spearman's rank correlation test. The expression levels of PD‑1 and PGE2 receptors were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The level of PD‑1 expression in infiltrating CD8+ T cells was gradually increased as the stage of lung cancer increased. The level of PD‑1 expression was also positively associated with the concentration of PGE2 in lung cancer tissues. Furthermore, the level of PD‑1 expression was closely associated with the PGE2/EP2 and PGE2/EP4 signaling pathways. The activation of PGE2‑associated EP2‑ and EP4‑pathways may positively regulate the level of PD‑1 in infiltrating CD8+ T cells, which results in immune tolerance in the lung cancer microenvironment.