自体肿瘤疫苗主动特异性免疫治疗对进展期肿瘤患者细胞免疫功能的影响

Effects of active immunotherapy with autologous tumor vaccine on cellular immune response in post-operative patients with advanced tumors

目的 探讨自体肿瘤疫苗的作用机制。方法 15例进展期肿瘤患者术后,以自体肿瘤疫苗辅助主动免疫治疗。术后第4周开始免疫接种(共4次,每次间隔7～10 d);接种前3 d及4次接种后1周,采集外周血,分离单个核细胞,测定CD8+-IFN-γ+,CD8+-IL-10+细胞比例及CD4+-IFN-γ+、CD4+-IL-10+细胞比例;同时采集血清检测血清IFN-γ、IL-10水平。结果 自体疫苗治疗后:①血清IFN-γ水平升高,由(6.08±2.79)pg/ml升至(12.31±5.42)pg/ml;而IL-10水平由(26.14±14.01)pg/ml降至(7.21±3.01)pg/ml,差异有显著性(P<0.05)。②CD8+-IFN-γ+双阳性细胞比例由(2.61±1.01)％升至(5.96±2.17)％;CD4+-IFN-γ+双阳性细胞比例由(3.25±1.52)％升至(6.20±3.87)％,差异有显著性(P<0.05)。③患者耐受性良好,无溃疡等严重不良反应发生。④临床随访10～26个月,15例患者无肿瘤复发或转移。结论 ①自体肿瘤疫苗可激发患者特异性细胞介导的免疫反应。②自体疫苗可改善患者的抗瘤免疫反应;③自体肿瘤疫苗主动特异性免疫治疗,对于杀灭残留癌细胞、抗转移及复发有重要作用。

Objective To explore the mechanism of active immunotherapy with autologous tumor vaccine. Methods Altogether 15 patients with advanced tumors were enrolled in this study.Four weeks after operation,the patients received autologous tumor vaccine every 7-10 days for 4 times as an adjuvant active immunotherapy. Three days before the first vaccination and 7 days after the last one: peripheral blood mononuclear cells(PBMC) were isolated to assay the alteration of the ratios between CD8+ -IFN-r+ and CD8+ -IHO+ ,and between CD4* -IFN-r+ and CD4+ -IL-10+ cells.Meanwhile,serum IFN-r and IL-10 was determined.Results After active immunotherapy with autologous tumor vaccine: 1 The serum IFN-r increased from (6.08 ±?2.79)pg/ml to(12.31 ± 5. 42)pg/ml(P<0.05)and the serum IL-10 decreased from(26.14() 14.01)pg/ml to(7.21 ±3.01)pg/ml(P < 0.05).The proportion of CD4+-IFN-r+ cells elevated from(3.25 ± 1.52)% to(6.20±3.87)%(P<0.05) ;2 The proportion of CD8+-IFN-r+ cells elevated from(2.61 ± 1.01)% to(5.96± 2.17)%(P< 0.05) ; 3 The patients tolerated well without serious side-effects such as ulceration;4 Follow-up study showed that the disease-free periods of the 15 patients were 10 to 26 months (still alive) .Conclusion The autologous tumor vaccine can elicit specific cellular immune response and improve host's anti-tumor immune response.It may play an important role in improving life quality, survival and prevention of recurrence and metastasis.