食管癌放疗中MICA-NKG2D系统功能变化与疗效的临床研究

A clinical study on system function and efficacy of MICA-NKG2D in radiation treatment for Esophageal cancer

目的探讨食管癌在放疗中MICA-NKG2D配受体功能变化，以及其变化与放疗疗效的关系。方法取食管鳞癌细胞株ECA109，用不同剂量照射后用流式细胞术检测MICA表达。采用ELISA法检测接受不同放疗剂量的食管癌患者血清中sMICA浓度，采用流式细胞术检测NK细胞NKG2D受体的表达，胞内染色法分析NK细胞杀伤靶细胞功能的变化，并在结束时及结束后4周，用WHO评价标准评价放疗疗效，研究NK细胞NKG2D受体的表达率提高与放疗疗效的关系。1年后评价生存率与NK细胞NKG2D受体的表达率提高的关系。结果食管鳞癌细胞株ECA109仅当32Gy的照射量才能诱导MICA明显表达并促进NK细胞对其的杀伤效应。放疗中食管癌患者血清内sMICA含量无明显变化，40～60gy的放疗剂量时NKG2D阳性的NK细胞数增加，同时其NK细胞毒活性最强。放疗前后NKG2D阳性的NK细胞数增加越高的放疗后疗效评价越好。但1年后的评价未证实此结论。结论放疗可以促使食管鳞癌细胞诱导MICA明显表达并促进NK细胞对其的杀伤效应。放疗中食管癌患者血清sMICA含量无明显变化，但放疗可使NKG2D阳性的NK细胞数增多，增加越明显的患者短期放疗疗效越好，但对远期1年生存率没有明显的影响。

Objective To study changes of the MICA-NKG2D ligand-receptor function in radiatio treatment Esophageal cancer, as well as the relationship between the changes and the efficacy of radiotherapy. Methods The effects of MICA expression on ECA-109 （esophageal squamous cell cancer） by a variety of doses of irradiation were detected by flow cytometry firstly. The concentration of serum sMICA protein from esophageal cancer patients by a variety of doses of irradiation were detected by ELISA. Next NKG2D expression on NK cells was measured by flow cytometry, and cytotoxicities were evaluated by intracellular staining with perforin antibody. The efficacy of radiotherapy was evaluated with the WHO evaluation criteria in the end. The relationship between the expression of NK cell receptor NKG2D and the efficacy of radiotherapy will be studied. the relationship between the expression of NK cell receptor NKG2D and survival rate will be studied after one year. Results Esophageal squamous carcinoma cell ECA109 induced expression of MICA and promoted of NK cell killing effect significantly only when it was exposed to 32 Gy. The sMICA serum concentration of patients with esophageal carcinoma by irradiation showed no significant change. The percentage of NK cells and their cytotoxicities increased with the dose of 40-60 Gy irradiation. Clinical evaluation was the higher percentage of NKG2D positive NK cells was increased, the better the efficacy of radiotherapy. However, the evaluation did not confirm this conclusion after a year. Conclusion Ridiotherapy cell can induce strong expression of MICA and significantly promote NK cell killing effect. The sMICA serum concentration of patients with esophageal carcinoma by irradiation showed no significant change. However, radiotherapy can increase the percentage of NKG2D positive NK cells. The higher percentage of NKG2D positive NK cells increase, the better short-term efficacy of radiotherapy in patients, but it had no significant effect for the long-term survival rate of one-year.