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

作者：Wang, Jinhong; Zhang, Li; Kang, Dong; Yang, Deguang^*; Tang, Ying^*

来源：Oncology Letters, 2018, 15(1): 552-558.

DOI：10.3892/ol.2017.7279

• lung cancer
• infiltrating T lymphocytes
• programmed cell death-1
• prostaglandin E2

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.

• 出版日期2018-1
• 单位南方医科大学; 吉林大学