Journal of Jilin University(Medicine Edition) ›› 2021, Vol. 47 ›› Issue (2): 249-256.doi: 10.13481/j.1671-587X.20210201

• Research in basic medicine •     Next Articles

Influence of PGE2 on PD-1 expression in infiltrating T lymphocytes in non-small cell lung cancer tissue and its mechanism

Ye YUAN1,Jinbao ZHUANG1,Xu SHI1,Changyuan LI2()   

  1. 1.Department of Laboratory,First Hospital,Jilin University,Changchun 130021,China
    2.Department of Thoracic Surgery,First Hospital,Jilin University,Changchun 130031,China
  • Received:2020-09-09 Online:2021-03-28 Published:2021-03-25
  • Contact: Changyuan LI E-mail:lichangyuanjlu@163.com

Abstract: Objective

To explore the expression of programmed death-1 (PD-1) in the infiltrating CD4+ and CD8+ T lymphocytes in non-small cell lung cancer (NSCLC) tissue, and to illuminate the influence of prostaglandin E2(PGE2) on the PD-1 expression and its related mechanism.

Methods

A total of 75 patients diagnosed as NSCLC were enrolled and divided into stages Ⅰ-Ⅳ according to the TNM staging criteria for NSCLC issued by the Union Internationale Against cancer (UICC).The infiltrating mononuclear cells in NSCLC tissue homogenate were separated by density gradient centrifugation. The percentages of CD4+ and CD8+ T lymphocytes in the infiltrating lymphocytes were analyzed by flow cytometry. Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blotting methods were used to detect the expression levels of PD-1 mRNA and protein in the infiltrating T lymphocytes. The PGE2 level in serum was detected by ELISA.

Results

The percentages of infiltrating CD8+ T lymphocytes in the NSCLC patients at stages Ⅲ and Ⅳ were obviously higher than those of the NSCLC patients at stages Ⅰ and Ⅱ(P<0.05), but the percentages of CD4+ T lymphocytes showed no significant differences among the patients at different stages(P>0.05). The expression level of PD-1 mRNA in the CD8+ T lymphocytes in the NSCLC patients at stage Ⅳ was higher than those of the patients at other stages (P<0.05), but the expression levels of PD-1 mRNA in the CD4+ T lymphocytes had no significant differences among the patients at different stages (P>0.05). The serum levels of PGE2 in the NSCLC patients at stages Ⅲ and Ⅳ were obviously higher than those in the NSCLC patients at stages Ⅰ and Ⅱ (P<0.05). The expression levels of EP2 and EP4 mRNA in the CD8+ T lymphocytes were obviously increased after PGE2 stimulating(P<0.05);the PD-1 mRNA expression levels in the CD8+ T lymphocytes were significantly decreased after adding EP2 and EP4 antagonists (P<0.05),and the PD-1 protein expression amounts were decreased.

Conclusion

PGE2 can promote the PD-1 expression in infiltrating CD8+ T lymphocytes in NSCLC tissue through PGE2/EP2 and PGE2/EP4 signaling pathways, resulting in the decreased immune function of CD8+ T lymphocytes.

Key words: cancer,non-small cell lung, T lymphocytes, programmed death-1, prostaglandin E2

CLC Number: 

  • R34