自体肿瘤疫苗主动特异性免疫治疗对结肠癌病人细胞免疫功能的影响

Effect of active specific immunotherapy with autologous tumor vaccine on cellular immune response in post-operative patients with colon cancer

目的 探讨自体肿瘤疫苗的作用机制。方法 2 0例结肠癌患者术后 ,以自体肿瘤疫苗行主动免疫治疗。术后第 4周开始免疫接种 (共 4次 ,每次间隔 7～ 10天 ) ;接种前 3天及 4次接种后 1周 ,采集外周血 ,分离单个核细胞 ,测定CD+ 8-IFN -γ+ ,CD+ 8-IL - 10 + ,细胞比例及CD+ 4 -IFN -γ+ 、CD+ 4-IL - 10 + 细胞比例 ;同时采集血清检测血清IFN -γ、IL - 10水平 ;用自体肿瘤抗原做皮肤迟发型过敏反应试验 ,4 8小时后测量红斑、硬结大小 (mm) ;临床随访。结果 自体疫苗治疗后 :血清IFN -γ水平升高 ,由 (6 .2 9± 1.96 )pg/ml升至 (10 .94± 3.2 1) pg/ml;而IL - 10水平由 (2 1.91± 10 .19)pg/ml降至(10 .84± 6 .0 1) pg/ml。有显著性差异 (P <0 .0 5 )。CD+ 8-IFN -γ+ 双阳性细胞比例由 (4.0 2± 1.13) %升至 (8.81± 2 .90 ) % ;CD+ 4 -IFN -γ+ 双阳性细胞比例由 (4.19± 1.10 ) %升至 (6 .99± 1.87) %。有显著性差异 (P <0 .0 5 )。治疗前后患者对自体肿瘤抗原的特异性DTH反应明显增强 (P <0 .0 1)。患者耐受性良好 ,无溃疡等严重副作用发生。 11例无瘤生存时间为 36～ 4 8个月 (仍健在 ) ;6例无瘤生存时间为 11～ 14个月 (仍健在 ) ;3例生存 2 4～ 2 6个月 (死于肝转移 )。

Objective To explore the mechanism of active immunotherapy with autologous tumor vaccine.Methods Twenty patients with colon cancer were enrolled in this study.Four weeks after operation,the patients received vaccinations of autologous tumor vaccine every 7～10 days for 4 times as adjuvant active specific immunotherapy,on 3rd day before and 7-th day after administrations peripheral blood monouclear cells (PBMC) were isolated to assay the alteration of proportions of CD + 8-IFN-γ + and CD + 8-IL-γ +,CD + 8-IFN-γ + and CD + 8-IL-γ + cell.Meanwhile,serum IFN-γand IL-10 were measured;within 48 hours after the skin test with autologous tumor antigen,diameters of erythemas or indurations were observed.The patients were followed-up.Results After active immunotherapy with autologous tumor vaccine,①the serum IFN-γ increased from(6.29±1.96)pg/ml to (10.94±3.21)pg/ml ( P <0.05).The proportion of CD + 8-IFN-γ + cell elevated from(4.02±1.13)% to (8.81±2.90)%( P <0.05);②The proportion of CD + 8-IFN-γ + cells elevated from(4.19±1.10)% to(6.99±1.87)%( P <0.05).③Specific DTH reactions to autologous tumor antigen enhanced obviously( P <0.05).④The patients tolerated well without serious side effects such as ulceration.⑤The results of follow-up showed that the disease-free interval of 11 patients were 36 to 48 months(still alive),6 patients survive for 11 to 14 months(still alive),3 patients survive for 24 to 26 months(died of hepatic metastases).Conclusion ①The autologous tumor vaccine can elicit specific cellular immune response.②It can improve the host's anti-tumor immune response.③It may play an important role in improving life quality survival and prevention of recurrence and metastasis.