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Authors Shen B, Qian A, Lao W, Li W, Chen X, Zhang B, Wang H, Yuan F, Sun Y
Received 26 January 2019
Accepted for publication 22 March 2019
Published 2 May 2019 Volume 2019:11 Pages 3909—3919
DOI https://doi.org/10.2147/CMAR.S203035
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 2
Editor who approved publication: Dr Beicheng Sun
Background: Many studies have shown that programmed
cell death protein 1 (PD-1) and its ligand, PD-L1, are expressed in advanced gastric cancer. Furthermore, detection of these proteins is associated with
infiltrating CD8+ T-cells, indicating that an adaptive immune resistance
mechanism occurs in advanced gastric cancer. However, PD-L1 and PD-1 expression
in gastric intraepithelial neoplasia and early-stage gastric cancer (EGC) has
yet to be elucidated.
Patients and methods: Fifty-four resections of low-grade intraepithelial neoplasia
(LGIN), high-grade intraepithelial neoplasia (HGIN), and EGC were stained by
immunohistochemistry for PD-1, PD-L1, and CD8. CD8+ T-cell densities both
within tumors and in the tumor-stromal interface were analyzed. Flow cytometry
(FACS) was used to analyze the PD-1 expression in tumor tissues and peripheral
blood mononuclear cells. Furthermore, the relationship between Helicobacter
pylori (Hp) infection and PD-1 and PD-L1 was also evaluated.
Results: We
demonstrated that PD-L1 expression was significantly increased in HGIN and EGC
compared with LGIN, and both PD-1 and PD-L1 showed similar expression patterns,
being mainly detected in infiltrating immune cells. FACS also showed that PD-1
was expressed on both CD4+ and CD8+ T-cells. However, no difference was found
in CD8+ T-cell infiltration between LGIN and HGIN+EGC, and this was not not
found to be associated with PD-L1 or PD-1 expression. However, Hp infection was
significantly associated with expression of PD-L1 and PD-1.
Conclusions: The
PD-1/PD-L1 checkpoint is involved in intraepithelial neoplasia and EGC, but an
adaptive immune resistance mechanism does not occur. Expression of PD-1/PD-L1
is also associated with Hp infection, and so Hp infection may be an important
initiating factor.
Clinical Trial Registration information: This study was approved by the Institutional
Review Board of Ruijin Hospital and written informed consent was obtained from
all patients.
Keywords: PD-L1,
PD-1, Helicobacter pylori, LGIN, HGIN