摘要
目的观察人自体原发性肝癌(以下简称"肝癌")组织提取的热休克蛋白70-肽复合物致敏的树突状细胞(HSP70-PC/DCs)瘤苗的免疫效应及其安全性。方法回顾性分析2010年2月至2015年2月期间我院和南通大学附属第三医院肝胆胰外科手术治疗的30例肝癌患者的临床病例资料,根据术后治疗方法分为HSP70-PC/DCs治疗组(免疫治疗组)和化疗组,每组15例。检测2组患者的外周血T淋巴细胞亚群、血清甲胎蛋白(AFP)及CA19-9水平,观察其毒副反应、复发、生存及KPS评分情况。结果 1 CD3+、CD4+、CD4+/CD8+及CD3CD56指标在治疗前的2组间比较差异无统计学意义(P>0.05);治疗后,以上指标在免疫治疗组均明显高于化疗组(P<0.05),且免疫治疗组治疗后较治疗前均有不同程度的升高且差异有统计学意义(P<0.05),而化疗组在治疗前、后比较差异无统计学意义(P>0.05)。2 AFP及CA19-9水平在治疗前的2组间比较差异无统计学意义(P>0.05);治疗后,以上指标在免疫治疗组均明显低于化疗组(P<0.05),且免疫治疗组治疗后以上指标均明显低于治疗前(t=2.564,P=0.021;t=2.011,P=0.041),化疗组以上指标治疗后较治疗前也有不同程度降低(t=2.221,P=0.036;t=2.487,P=0.066)。3免疫治疗后,有3例患者出现发热(体温38.0~38.5℃),未给予特殊处理,体温均在5~24 h内恢复正常。有2例患者瘤苗注射局部出现直径1.0~1.5 cm的皮肤红肿,患者均可耐受,未予特殊处理,72 h后皮肤红晕消散。瘤苗接种期间,患者均未出现恶心、呕吐、头痛等症状,1例患者出现肌肉痛,给予吲哚美辛后疼痛消失,部分患者出现不同程度的食欲改善,疼痛缓解,生存质量得到明显改善,血常规及肝功能检测也未发现明显异常,所有患者耐受性良好。4 30例患者随访时间5~19个月,中位随访时间9个月。免疫治疗组共死亡4例,中位生存时间为560 d,化疗组中位生存时间为436 d。治疗后,免疫治疗组的KPS评分明显高于化疗组(t=2.421,P=0.045),免疫治疗组的复发率明显低于化疗组(χ~2=0.651,P=0.048),免疫治疗组和化疗组的总生存率比较差异无统计学意义(χ~2=0.476,P=0.579)。结论从本组有限的数据初步可见,应用HSP70-PC/DCs瘤苗对肝癌的治疗是安全、有效的,对激活T淋巴细胞抑制肿瘤生长可能有效,可提高免疫力及预防术后复发。
Objective To investigate immunological therapeutic effect and safety of dendritic cells （DCs） combined with heat shock protein 70 （HSP70）-peptide complex （PC） derived from autogeneic hepatoma tissue. Methods Thirty patients with hepatocellular carcinoma from February 2010 to February 2015 in the Gaochun People＇s Hospital of Nanjing and The Third Affiliated Hospital of Nantong University were studied, and subsequently were divided into an immunotherapy group （treated with HSP70-PC/DCs vaccine, n=15） and a chemotherapy group （n=15） according to the prescribed postoperative treatment methods. The Jevels of T lymphocyte subtypes were assayed by FACS. The toxicity adverse reactions, alpha-fetoprotein （AFP）, CA19-9, hepatic tumor recurrence rate, survival rate, and KPS of two groups patients were evaluated and compared between these two groups. Results② The values of CD3＋, CD4＋, CD4＋/CD8＋, and CD3CD56 had no significant differences between the immunotherapy group and the chemotherapy group before treatment （P〉0.05）, which in the immunotherapy group were significantly higher than those in the chemotherapy group after treatment （P〈0.05）, and which were significantly higher in the immunotherapy group after treatment as compared with the levels before treatment （P〈0.05）, and which had no significant differences in the chemotherapy group between after treatment and before treatment （P〉0.05）. ② Before treatment, the levels of AFP and CA19-9 had no significant differences between the immunotherapy group and the chemotherapy group （P〉0.05）, which in the immunotherapy group were significantly lower than those in the chemotherapy group after treatment （P〈0.05）. In the immunotherapy group, the levels of AFP and CA19-9 after treatment were significantly lower than those before treatment （t=2.564, P=0.021; t=2.011, P=0.041）, which in the chemotherapy group before treatment were decreased as compared with the levels before treatment （t=2.221, P=0.036; t=2.487, P=0.066）. ③The patients treated with the HSP-PC/DCs vaccines was well tolerated and no obvious toxicity was appeared.④ All the patients were followed up 5-19 months with median follow-up time of 9 months. The median survival time was 560 d and 436 d in the immunotherapy group and the chemotherapy group, respectively. After treatment, KPS score was significantly higher and recurrence rate was significantly lower in the immunotherapy group as compared with the chemotherapy group （P〈0.05）. The total survival had no significant difference between the immunotherapy group and the chemotherapy group （P〉0.05）. Conclusions The preliminary results of limited cases in this study show that HSP70-PC/DC vaccination is safe and effective in treatment of hepatocellular carcinoma, the pulsed DCs are effective in activating specific T-cell responses against hepatocellular carcinoma cells. HSP70-PC/DC vaccine might improve immunity and prevent postoperative recurrence of hepatocellular carcinoma.
出处
《中国普外基础与临床杂志》
CAS
2017年第2期222-227,共6页
Chinese Journal of Bases and Clinics In General Surgery
