Immunoregulatory Function of HLA-G in Gastric Cancer

Abstract

<b>Background:</b> Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poorsurvival, but links with tumor escape mechanisms remain to be determined. Materials and <br/><b>Methods</b>: We usedimmunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Tregcells in 52 gastric cancer patients. <br/><b>Results</b>: There were 29 cancer-related deaths during the follow-up period.Kaplan-Meier analysis indicated that patients with HLA-G-positive (n=16) primary tumors had a significantlypoorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+Tlymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and highnumbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysisshowed that HLA-G expression (hazard ratio: 2.662; 95% confidence interval: 1.242-5.723; p=0.012) and stage(hazard ratio: 2.012;95% confidence interval: 1.112-3.715; p=0.041) were independent unfavorable factors forpatient survival. <br/><b>Conclusions</b>: We found a significant positive correlation between HLA-G expression and thenumber of tumor infiltrating Tregs (p=0.01) and a negative correlation with the number of CD8+T lymphocytes(p=0.041). HLA-G may protect gastric cancer cells from cytolysis by inducing Foxp3+Treg lymphocytes andsuppressing CD8+T lymphocytes.