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Liu S.,Fujian Provincial Tumor Hospital | Zhou Z.,Fujian Key Laboratory of Translational Cancer Medicine | Zhou Z.,Tumor Immunology Laboratory of Fujian Provincial Tumor Hospital | Zheng Q.,Fujian Provincial Tumor Hospital | And 5 more authors.
Chinese Journal of Clinical Oncology | Year: 2013

Objective: This work aims to evaluate MHC class I chain-related gene A (MICA) expression on the cell membrane of esophageal cancer cells, and soluble MICA expression in the serum of patients with esophageal cancer. The work also aims to investigate the function of MICA in esophageal cancer. Methods: Flow cytometry was performed to detect the expressions of membranous MICA (mMICA) in esophageal cancer tissues and cell lines and natural-killer group 2, member D (NKG2D) in natural killer (NK) cells. En zyme-linked immunosorbent assay was performed to examine the secretion of soluble MICA (sMICA) in the peripheral blood. The effect of sMICA on NKG2D expression was observed in the group experiments. Results: mMICA was not detected in normal esophageal tissues, but the mMICA expression level was 31.7% in esophageal cancer tissues. The maximum expression level was (42.2 ± 3.6)%. sMICA was not detected in the serum of healthy subjects, but the sMICA expression level was 74.67% in esophageal cancer tissues with a concentration of (1977.30 ± 292.67)ng/L. A positive correlation was observed between sMICA levels and esophageal cancer stage. sMICA content was higher in cancer patients with distant metastasis compared with those without metastasis. However, the content had no relationship with nodal metastasis and pathologic types. NKG2D expression was down-regulated, and the NK cell cytotoxicity to the esophageal cancer cell line ECA-109 decreased after the NK cells were cultured in sMICA serum. Conclusion: MICA is expressed on the membrane of some esophageal cells. sMICA level is positively correlated with the Tumor-Node-metastasis stages of esophageal cancer. sMICA can reduce the expression of NKG2D and can result in immunity to esophageal cancer. Source


Zhou Z.,Tumor Immunology Laboratory of Fujian Provincial Tumor Hospital | Li J.,Tumor Immunology Laboratory of Fujian Provincial Tumor Hospital | Chen M.,Tumor Immunology Laboratory of Fujian Provincial Tumor Hospital | Ye Y.,Tumor Immunology Laboratory of Fujian Provincial Tumor Hospital
Chinese Journal of Clinical Oncology | Year: 2013

Objective: To explore the role of NKG2D ligand MHC-I related molecule A (MICA) in chemotherapy combined with NK cell immunotherapy in patients with advanced esophageal cancer after surgery. Methods: A total of 90 patients with esophageal cancer from Fujian Provincial Tumor Hospital were divided into three groups after surgery: 40 patients of chemotherapy alone, 25 patients of chemotherapy combined with NK cell therapy with negative expression of MICA (MICA- group), and 25 patients of chemotherapy combined with NK cells therapy with positive expression of MICA (MICA+ group). The efficacy was then compared. Results: Compared with the chemotherapy alone and MICA - groups, the positive rates of CD3+, CD4+ T cells, NK cells, and the CD4+/CD8+ ratio in peripheral blood from MICA+ group were higher than those before treatment (64.2% ± 6.4% vs. 51.3% ± 5.6%, 39.8% ± 8.2% vs. 29.5% ± 3.2%, 25.3% ± 2.1% vs. 16.4% ±4.3%, 1.4% ± 0.5% vs. 1.1% ± 0.7%; P<0.05). Meanwhile, the levels of T-reg cells were lower than those before treatment (6.3% ± 4.5% vs. 17.3% ± 2.4%, P<0.05). No significant difference was observed between the disease control rate and response rate. Chemotherapy-induced neutropenia and peripheral neurotoxicity symptoms were significantly improved, and time to progression (TTP) and overall survival (OS) were significantly prolonged (P<0.05). No statistically significant difference was observed between the chemotherapy alone group and MICA-group (P>0.05). Conclusion: Treatment with chemotherapy and autologous NK cells on patients with advanced esophageal carcinoma and MICA positive expression can be safely transfused with only minor side effects and can effectively improve a patient's immune system, quality of life, and survival. Source

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