BACKGROUND: Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined. MATERIALS AND METHODS: We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancer patients. RESULTS: 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 significantly poorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysis showed 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 for patient survival. CONCLUSIONS: We found a significant positive correlation between HLA-G expression and the number 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 and suppressing CD8+T lymphocytes.
BACKGROUND:Humanleukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined. MATERIALS AND METHODS: We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancerpatients. RESULTS: 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 significantly poorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysis showed 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 for patient survival. CONCLUSIONS: We found a significant positive correlation between HLA-G expression and the number 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 and suppressing CD8+T lymphocytes.
Authors: Fabrício C Dias; Erick C Castelli; Cristhianna V A Collares; Philippe Moreau; Eduardo A Donadi Journal: Front Immunol Date: 2015-02-02 Impact factor: 7.561