MHC-Ⅰ类相关分子A表达在食管癌患者术后自然杀伤细胞免疫治疗中的作用

Role of MHC class I -related molecules A on NK cells immunotherapy in esophageal cancer patients after operation

目的探讨MHC—I类相关分子A（MICA）分子表达与早期食管癌患者术后自然杀伤（NK）细胞过继免疫治疗的相关性，并分析MICA表达在NK细胞治疗中的意义。方法100例食管癌患者分为单纯手术组40例、MICA阴性NK细胞治疗组（MICA一组）30例及MICA阳性NK细胞治疗组（MICA＋组）30例，分别于手术前及手术后60d检测患者外周血CD3＋、CD4＋、CD4＋／CD8＋、NK细胞比例、调节性T细胞（Treg细胞）比例、Thl／Th2／Thl7细胞因子水平、血清抗体IgA、IgM、IgG以及肿瘤标志物CEA、SCC、CAl99、CYFRA21．1等的变化，初步评价患者近期疗效。结果MICA＋组患者外周血CD3＋、CD4＋、NK细胞阳性率及CD4＋／CD8＋比例明显高于治疗前[（68.3±7．6）％比（56．2±4．1）％，（39．8±8．2）％比（30．8±4．7）％，（22．2±4．7）％比（18．7±5．5）％，（1．49±0．30）比（1．15±0．61）；均P〈0．051，Treg细胞阳性率明显低于治疗前[（8．1±4．0）％比（13．4±4．5）％，P〈0．05]，CD；细胞阳性率治疗前后差异无统计学意义[（26．9±6．2）％比（27．8±7．1）％，P〉0．05]。MICA＋组患者外周血中Thl类细胞因子（包括IL-2、IFN-1和TNF-α）水平增高，Th2类细胞因子（IL-4、IL-6、1L-10）水平降低（P〈0．05），但Thl7细胞因子水平差异无统计学意义（P〉0．05）。同时提高IgA、IgM、IgG含量，但NK细胞治疗前后肿瘤标志物CEA、SCC、CA199、CYFRA21-1差异无统计学意义（P〉0．05）。结论早期食管癌组织MICA表达阳性患者进行NK细胞过继免疫治疗能有效提高细胞免疫及体液免疫水平。

Objective To explore the relevance of expression of MHC class I -related molecules A （MICA） molecule and NK cells immunotherapy in esophageal cancer patients after operation. To analyze the significance of MICA expression in NK cell immunotherapy. Methods 100 patients of esophageal cancer were divided into 3 group, surgical alone group, MICA negative with NK therapy group （MICA- group） and MICA positive with NK therapy group （MICA＋ group）. The immunity indicators and tumor markers including the levels of CD3＋, CD4＋ T cells, ratio of CD：/CDL NK cells, Treg cells, the levels of Thl/Th2/Thl7 cytokine, the antibody IgA, IgM, IgG and the tumor markers of CEA, SCC, CA199, CYFRA21-1 were detected before treatment and after treatment 60 days. Results The positives rates of CD3＋, CD4＋ T cells, NK cells and the ratio of CD4＋/CD8＋ in peripheral blood from MICA＋ patients group were higher than those of before treatment [（68.3±7.6） % vs （56.2±4.1） %, （39.8±8.2） % vs （30.8±4.7） %, （22.2±4.7） % vs （18.7±5,5） %, （1.49±0.30） vs （1.15±0.61）, P 〈 0.05], meanwhile the levels of Treg cells was lower than those of before treatment [（8.1±4.0） % vs （13.4±4.5） %, P 〈 0.05]. There was no statistical significant difference of positive rate of CD8＋ T cells [（26.9±6.2） % vs （27.8±7.1） %, P 〉 0.05]. The levels of Thl eytokin （IL-2, IFN-~ and TNF-ct） increased and Th2 cytokin （IL-4, IL-6 and IL-10） decreased after treatment. The level of Thl7 cytokine was not different significantly （P 〉 0.05）. The content of IgA, IgM, IgG in MICA＋ group were effectively improved after treatment. The tumor markers CEA, SCC, CA199, CYFRA21-1 had no statistically change before and after treatment. Conclusion The results indicate that NK cells immunotherapy can enhance the cellular immunity and humoral immunity of MICA positive esophageal cancer patients after operation.