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Oncol Lett. 2018 Jan;15(1):552-558. doi: 10.3892/ol.2017.7279. Epub 2017 Oct 26.

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.

Author information

1
Respiratory Department, The Third Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China.
2
Department of Nephrology, The First Hospital of Jilin University, Changchun, Jilin 130000, P.R. China.
3
Huiqiao Department, South Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China.
4
Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China.
5
Department of Respiration, The First Hospital, Jilin University, Changchun, Jilin 130000, P.R. China.

Abstract

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.

KEYWORDS:

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

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