<p>Relationship between Helicobacter pylori and expression of programmed death-1 and its ligand in gastric intraepithelial neoplasia and early-stage gastric cancer</p>

Abstract

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.

ARID1A knockdown enhances carcinogenesis features and aggressiveness of Caco-2 colon cancer cells: An in vitro cellular mechanism study

“…Resistance to the cell death is one of the important characteristic features of the cancer cells. Additionally, the association between high-grade staging and cell death resistance has been reported in several cancers [44][45][46][47]. Interestingly, inactivation of SWI/SNF complex by ARID1A mutation has been reported to be associated with the decreased cell death in ovarian cancer cells [48].…”

Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients

“…Furthermore, PD-L1 expression on tumor-infiltrating immune cells was reported to be associated with distinct clinicopathological features, including high densities of tumor-infiltrating lymphocytes, mismatch repair deficiency, and EBV positivity in GC [33]. Helicobacter pylori infection, known as the strongest risk factor for GC, was also significantly associated with expression of PD-L1 and PD-1 [34]. However, the correlations among the frequency of PD-1 + macrophages, mismatch repair deficiency, and EBV and Helicobacter pylori infection remains unclear in this study.…”

Role of PD-L1 Expression during the Progression of Submucosal Gastric Cancer

“…In this study, we did not observe a correlation between the expression of PD-L1 in cancer cells and that in other proteins. Shen et al [35] revealed that there was no correlation with CD8 and PD-L1, suggesting that an adaptive immune resistance mechanism may be inactive in early-stage cancer. Okabe et al [36] reported that CD8 + T cell density was not associated with PD-L1 expression in early breast cancer.…”