NKG2D配体在中晚期食管癌患者术后NK细胞免疫治疗中的作用

Role of NKG2D ligand on NK cell immunotherapy in advanced esophageal cancer patients after operation

目的:探讨NKG2D配体MHC-I类相关分子A(MHC class I-related molecules A,MICA)在中晚期食管癌患者术后化疗联合NK细胞免疫治疗中的作用。方法:福建省肿瘤医院90例中晚期食管癌患者手术后,分为单纯化疗组40例、化疗联合NK细胞治疗MCIA阴性组(简称MICA-组)25例及化疗联合NK细胞治疗MICA阳性组(简称MICA+组)25例,比较其疗效。结果:与单纯化疗组及MICA-组相比,MICA+组CD3+、CD4+T细胞阳性率、NK细胞阳性率及CD4+/CD8+比率明显高于治疗前[(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);均P<0.05],T-reg细胞明显低于治疗前[(6.3±4.5)%vs(17.3±2.4)%,P<0.05]。3组疾病控制率及有效率无明显差异(P>0.05)。MICA+组KPS评分治疗后明显提高,MICA+组能明显改善化疗引起的白细胞减少、外周神经毒性症状,MICA+组疾病进展时间(time to progression,TTP)及总体生存时间(overall survival,OS)均明显延长(均P<0.05)。但单纯化疗组及MICA-组之间差异无统计学意义(P>0.05)。结论:食管癌组织MICA表达阳性的中晚期患者进行化疗联合自体NK细胞能有效能有效提高免疫力,改善患者生活质量,并能延长生存期,且回输安全、不良反应小。

Objective： To explore the role ofNKG2D 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.