Abstract
Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined. We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancer patients. 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. 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.
Highlights
Human leukocyte antigen (HLA)-G is an MHC class I antigen expressed primarily in the placenta
HLA-G, a non-classic MHC class I protein was first observed on extravillous cytotrophoblasts, thymic epithelial cells that play an important role in immune tolerance during pregnancy
HLA-G expression was demonstrated in melanoma in 1998 (Paul et al, 1998)
Summary
HLA-G is an MHC class I antigen expressed primarily in the placenta. It modulates the immune tolerance of the mother (Guo et al, 2013). HLA-G expression is associated with aggressive tumor behavior and poor survival in patients with gastric cancer (Yie et al, 2007). HLA-G associated immune escape in gastric cancer is mediated by increasing local Foxp3+ regulatory T (Treg) cells (Du et al, 2011). We investigated HLA-G expression and its relationship with tumor infiltrating CD8+ T lymphocytes, Tregs, and clinicopathologic parameters in patients with gastric cancer. 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. 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
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