自体树突状细胞疫苗诱导胃癌患者术后肿瘤特异性免疫反应的作用

Tumor specific immune response in postoperative gastric cancer patients induced by dendritic cells vaccine

目的探讨胃癌术后患者应用树突状细胞(dendriticcells,DCs)疫苗治疗后机体肿瘤特异性免疫反应的变化。方法采用外周血单个核细胞及自体肿瘤抗原在体外制备DCs疫苗,皮下注射胃癌术后患者,每周1次,共治疗4次。在治疗前后相应各时相点检测针对自体肿瘤抗原的迟发性超敏反应(delayedtypehypersensitivity,DTH),外周血单个核细胞混合淋巴细胞反应(mixedlymphocytereacion,MLR)及细胞上清IFNγ及IL4的水平。结果疫苗治疗后可以明提高外周血单个核细胞混合淋巴细胞反应的强度。治疗前及治疗后第2、4、8周患者外周血单核细胞(peripheralbloodmonocytecell,PBMC)分泌IFNγ的水平分别为(184±20)、(467±55)、(700±88)、(257±38)pg/ml,各组差异显著;而分泌IL4的水平分别为(66±8)、(69±9)、(66±7)、(61±7)pg/ml。各组之间无明显变化。有16例疫苗注射后患者DTH反应呈阳性。结论树突状细胞疫苗可改善胃癌术后患者免疫功能状态,并诱导出了肿瘤特异性的免疫反应。

Objective To investigate tumor specific immune response in postoperative patients with gastric cancer induced by dendritic cells vaccine. Methods Dendritic cells were produced and pulsed with self tumor antigens in vitro. Twenty-five patients with gastric cancer were treated with DCs vaccinations. DCs vaccine was administered subcutaneously once a week for 4 times to the postoperative patients after they finished chemotherapy. PBMC mixed lymphocyte reactions （MLR） and delayed-type hypersensitivity （DTH） reactions to self tumor lysates were measured in vitro before and after the vaccinations. Results The level of IFN-γreleased by PB- MC of patients were （184 ±20）, （467 ±55）, （700 ±88）, （257 ±38） pg/ml before and 2, 4 and 8 weeks after vaccination respectively and IL-4 level was （66 ± 8 ）, （69 ± 9 ）, （ 66 ± 7 ）, （ 61 ± 7 ） pg/ml. The intensity of MLR and the level of IFN-γ in PBMC supernatant increased significantly after vaccination, while the IL-4 level in PBMC supernatant had no significant changes. Sixteen patients developed delayed type hypersensitivity reactions to tumor lysates after immunization. Conclusion The dendritic cells vaccine can induce antigen specific immunity in postoperative patients with gastric cancer.