RRC ID 38497
Author Du L, Xiao X, Wang C, Zhang X, Zheng N, Wang L, Zhang X, Li W, Wang S, Dong Z.
Title Human leukocyte antigen-G is closely associated with tumor immune escape in gastric cancer by increasing local regulatory T cells.
Journal Cancer Sci
Abstract 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.
Volume 102(7)
Pages 1272-80
Published 2011-7-1
DOI 10.1111/j.1349-7006.2011.01951.x
PMID 21466615
MeSH Adult Aged Cell Line, Tumor Cytokines / biosynthesis Female HLA Antigens / blood HLA Antigens / physiology* HLA-G Antigens Histocompatibility Antigens Class I / blood Histocompatibility Antigens Class I / physiology* Humans Male Middle Aged Prognosis Stomach Neoplasms / immunology* Stomach Neoplasms / mortality T-Lymphocytes, Regulatory / immunology* Tumor Escape*
IF 4.966
Times Cited 46
Human and Animal Cells MKN45(RCB1001) MKN28(RCB1000) HGC-27(RCB0500)