结直肠癌化疗联合自体多种免疫细胞治疗疗效观察

Clinical effects of treatment with comprehensive multipe autologous immune cells in patients with coclorectal carcinoma

目的比较结直肠癌患者自体多种免疫细胞联合化疗与单纯化疗后细胞免疫功能变化和生存期差异。方法83例结直肠癌患者分为化疗组43例，化疗联合自身多种免疫细胞治疗组（联合组）40例；用血细胞分离机采集患者自身外周血单个核细胞（PBMC），将PBMC按常规方法分别诱导培养CD3AK细胞、CIK细胞、树突状细胞（DC）、7gT细胞和NK细胞；用流式细胞仪检测治疗前后患者外周血的CD3（＋）、CD4（＋）、CD8（＋）、CD19（＋）、CD16（＋）CD56（＋）、CD4／CD8和3,gT细胞比值及PBMC中穿孑L素、颗粒酶B和CD107a阳性表达率。2组患者化疗方案都采用草酸铂＋亚叶酸钙＋5-氟脲嘧啶静脉输注；联合组在化疗基础上接受免疫细胞治疗。结果联合组治疗后的免疫细胞亚群比值和绝对值显著高于化疗组。联合组与化疗组Karnofsky评分差异有统计学意义。联合组患者治疗后PBMC的穿孔素、颗粒酶B及CDl07a均高于治疗前，并且治疗后这3种指标数值均皿著高于化疗组。联合组患者1午、2年和5年生存率分别为70．o％、20．0％和10．0％，高于化疗组（分别为23．2％、7．0％和4．6％）；其中Ⅱ期、Ⅲ期患者的1年、2年和5年生存率及Ⅳ期患者的1午生存率2组间比较差异有统计学意义，而Ⅳ期患者的2年、5年生存率2组间比较差异无统计学意义。结论化疗联合自身综合性免疫细胞治疗进展期结直肠癌能提高患者的免疫功能，延长生存期。

Objective To compare the changes of immune functions and survival time in patients with colorectal carcinoma after the treatments of adoptive immunotherapy with comprehensive multiple autologous immune cells combined with chemotherapy and chemotherapy alone. Methods Eighty - three patients with eolorectal carcinoma were randomized into chemotherapy group （ n = 43 ） and chemotherapy combined with comprehensive adoptive immunotherapy group （ n = 40 ）. Peripheral blood mononuclear cells （PBMC） from the patients were collected by blood cell separator and sepa- rately cultured into CD3AK, CIK, dendritic cell （DC）, yST, NK and NKT cells by conventional methods; cell ratios of CD3（ ＋ ） ,CD4（ ＋ ） ,CD8（ ＋ ） ,CD19（ ＋ ） ,CD16（ ＋ ） CD56（ ＋ ） ,CD4/CD8 and ySY in peripheral blood and positive expression rates of pefforin,granzyme B and CD107a in PBMC before and after treatment were detected by flow cytometry. Treatlnent ：the chemotherapy regimen of all the patients was oxaliplatin plus CF and 5 - FU, on the basis of chemotherapy, combination group accepted comprehensive autologous adoptive immunotherapy. Results After the treatment, the immunocyte subsets of combination group were significantly higher than those of chemotherapy group. The scores of Karnofsky in both groups were statistically significant. After the treatments, the positive rates of perforin,granzyme B and CD107a in combination group were obviously elevated and higher than those of chemotherapy group. The overall 1, 2 and 5 - year survival rates of patients （ stage Ⅱ ,Ⅲ and Ⅳ ） in combination group were 70.0% ,20.0% and 10.0% , higher than those of chemotherapy group （23.2% ,7.0% and 4.6% , respectively）. Between the two groups, significant difference was found on 1, 2 and 5 - year survival rate of stage Ⅱ , m patients and 1 - year survival rate of stage Ⅳ patients, no significant difference was found in 2 and 5 - year survival rate of stage Ⅳ patients. Conclusion For advanced colorectal carcinoma patients, chemotherapy combined with comprehensive autologous adoptive immunotherapy can enhance their immunological function and prolong their survival duration.