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

摘要

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.