Human Leukocyte Antigen-G Inhibits the Anti-Tumor Effect of Natural Killer Cells via Immunoglobulin-Like Transcript 2 in Gastric Cancer
| Autor: | Xu-Dong Peng, Rui Wan, Jun-Ming Ou, Ziwei Wang, Hui Li, Guangyi Liu, Anqi Cheng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Physiology Mice SCID Lymphocyte Activation lcsh:Physiology Leukocyte Immunoglobulin-like Receptor B1 0302 clinical medicine Mice Inbred NOD HLA-G Cytotoxic T cell Hla-G lcsh:QD415-436 Receptor biology medicine.diagnostic_test lcsh:QP1-981 Chemistry Middle Aged Prognosis Killer Cells Natural medicine.anatomical_structure Receptors KIR2DL4 030220 oncology & carcinogenesis Female Antibody ILT2 Transplantation Heterologous Tumor escape Natural killer cell Disease-Free Survival Flow cytometry lcsh:Biochemistry Interferon-gamma 03 medical and health sciences Antigens CD Stomach Neoplasms Cell Line Tumor medicine Animals Humans Aged Cell Proliferation HLA-G Antigens Tumor Necrosis Factor-alpha Cell growth Coculture Techniques 030104 developmental biology Cell culture biology.protein Cancer research Gastric cancer |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 44, Iss 5, Pp 1828-1841 (2017) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: Human leukocyte antigen-G (HLA-G) plays an important role in inhibiting natural killer (NK) cell function and promoting immune escape. However, the specific mechanism of HLA-G on NK in gastric cancer (GC) remains not well understood. This study investigated the expression of HLA-G in GC and the role of HLA-G-effected NK cells in GC progression. Methods: HLA-G expression in GC tissues obtained from 49 patients with GC was analyzed by immunohistochemistry and western blot. The number of tumor-infiltrating NK cells and the expression of their surface receptors were analyzed by immunohistochemistry and flow cytometry, respectively. The effect of HLA-G on NK cell proliferation was examined by Cell Counting Kit-8 (CCK8) assay. LDH release assay was used to evaluate the effect of HLA-G on the cytotoxic activity of NK cells, and the levels of IFN-γ and TNF-α in the co-cultured supernatant were detected by ELISA. Mice bearing a xenograft tumor model were used to examine the effect of HLA-G on the anti-tumor effect of NK cells. Results: HLA-G positive expression was detected in most of the GC tissues, and was correlated with the adverse prognosis of the disease. The expression of HLA-G was negatively associated with the number of tumor-infiltrating NK cells. Furthermore, GC cell lines with overexpressed HLA-G revealed their ability to inhibit the cell proliferation and cytotoxic activity of NK-92MI cells, and reduce the secretion of IFN-γ and TNF-α through immunoglobulin-like transcript 2 (ILT2). Finally, this in vivo experiment was able to prove that HLA-G can inhibit the anti-tumor effect of NK cells through ILT2. Conclusion: The expression of HLA-G was strongly correlated with the adverse prognosis of GC. The reason may be that it inhibits the proliferation and cytotoxic activity of infiltrating NK cells through ILT2. |
| Databáze: | OpenAIRE |
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