Open AccessHuman leukocyte antigen‐G is closely associated with tumor immune escape in gastric cancer by increasing local regulatory T cells
Author(s) -
Du Lutao,
Xiao Xiaoyan,
Wang Chuanxin,
Zhang Xuhua,
Zheng Ni,
Wang Lili,
Zhang Xin,
Li Wei,
Wang Shun,
Dong Zhaogang
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.01951.x
Subject(s) - immune system , human leukocyte antigen , immunology , cancer , hla g , tumor necrosis factor alpha , antigen , peripheral blood mononuclear cell , immunotherapy , cancer research , biology , medicine , in vitro , biochemistry
Human leukocyte antigen‐G (HLA‐G) plays an important role in tumor cell escape. We investigated HLA‐G expression and regulatory T cells (Tregs) infiltrates in patients with gastric cancer (GC), analyzed their relationship with clinicopathologic features, and characterized their role in tumor immune escape. We also investigated the plasma soluble HLA‐G level and its potential in the diagnosis of GC. Effect of HLA‐G on Tregs was further assessed by coculture experiments in vitro . Most interestingly, HLA‐G positive expression was detected in GC tissues and it was significantly correlated with the presence of tumor‐infiltrating Tregs. Patients with HLA‐G positive expression or high Tregs had significantly poorer survival at 5 years after operation. Multivariate analysis indicated that HLA‐G positive expression was an independent prognostic factor of GC. The coculture experiment showed overexpression of HLA‐G in GC cell lines significantly enhanced the frequency of Tregs when GC cells were directly cocultured with human peripheral blood mononuclear cell. However, this effect disappeared when the indirect coculture system was applied. Some cytokines such as interleukin‐6, interleukin‐10, and tumor necrosis factor‐α significantly changed in the coculture system. Moreover, plasma soluble HLA‐G level in GC patients was higher than that in normal controls. Taken together, our results indicated that HLA‐G expression was closely associated with tumor progression and involved in tumor evasion by increasing the frequency of infiltrating Tregs locally. Thus, HLA‐G might be a promising predictor for disease prognosis and a possible novel target for immunotherapy in GC patients. ( Cancer Sci 2011; 102: 1272–1280)