研究実績の概要 |
Introduction. Anti-programmed cell death 1 (PD-1) therapies have shown promising clinical activity against gastric cancer (GC). We evaluated the clinical significance of immune-related gene expression in GC tissues to better understand the tumor immune microenvironment. Methods. PD-1, PD-1 ligand 1 (PD-L1) and CD8 mRNA levels and clinicopathological factors, including survival, were examined by quantitative RT-PCR in 155 GC patients who underwent surgery. PD-1 and PD-L1 expression in tumor tissue from 24 GC patients was investigated by immunohistochemical analysis. Results. PD-1, PD-L1 and CD8 mRNA levels were significantly lower in tumor tissue than in normal tissue (P < 0.0001, P < 0.05, and P < 0.0001). GC patients with low PD-1, PD-L1 and CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD-1, PD-L1 and CD8 mRNA levels, respectively (P < 0.001, P < 0.01 and P < 0.05). Multivariate analysis showed that lymph node metastasis, peritoneal dissemination, distant metastasis, low PD-1 mRNA levels and low CD8 mRNA levels were independent prognostic factors for worse OS (low PD-1 mRNA level: OR 2.16, 95% CI 1.10-4.58, P < 0.05; low CD8 mRNA level: OR 2.55, 95% CI 1.12-6.90, P < 0.05). PD-1 and PD-L1 mRNA levels in immune cells were significantly associated with PD-1 and PD-L1 protein levels (both P < 0.05), respectively. Conclusions. PD-1, PD-L1 and CD8 mRNA levels may reflect antitumor immunity in GC, and low PD-1 and CD8 mRNA levels are potential predictive biomarkers for poor prognosis in GC patients who underwent surgery.
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