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.
[1]Southern Med Univ, Hosp 3, Resp Dept, Guangzhou 510630, Guangdong, Peoples R China.
[2]Jilin Univ, Hosp 1, Dept Nephrol, Changchun 130000, Jilin, Peoples R China.
[3]Southern Med Univ, South Hosp, Huiqiao Dept, Guangzhou 510630, Guangdong, Peoples R China.
[4]Southern Med Univ, Affiliated Hosp 3, Dept Cardiol, 183 Zhongshan St, Guangzhou 510630, Guangdong, Peoples R China.
[5]Jilin Univ, Hosp 1, Dept Respirat, 71 Xinmin St, Changchun 130000, Jilin, Peoples R China.
(8.0+极速模式)