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
|
WOS Category
|
ONCOLOGY
|
Resource |
Human and Animal Cells |
MKN45(RCB1001)
MKN28(RCB1000)
HGC-27(RCB0500) |