自体CIK细胞治疗21例中晚期恶性实体瘤的肿瘤标志物变化观察

Self-derived cytokine-induced killer cells for patients with advanced malignant solid tumors

目的观察自体细胞因子诱导的杀伤细胞(CIK)过继免疫疗法治疗中晚期恶性实体肿瘤的临床疗效及肿瘤标志物变化,初步对该疗法作出评价。方法取中晚期恶性实体肿瘤患者自体外周血50ml,根据文献报道方法体外诱导扩增CIK细胞。培养约14d后,一次性回输入患者体内,观察患者CIK细胞回输前2周及回输后4周左右外周血免疫指标变化、肿瘤标志物变化、生活质量及Karnofsky评分变化,随访1年观察1年生存率。采用t检验及寿命表法进行统计分析。结果在21例接受CIK回输治疗的患者中,治疗前出现有代表意义的肿瘤标志物异常升高的患者有14例,1次回输后有8名患者出现肿瘤标志物下降,其中1名患者降至正常范围;免疫指标在CIK细胞回输后4周较回输前2周均无有统计学意义,其中CD3由70.81﹪±10.52﹪升至71.91﹪±11.09﹪,t=0.762,P=0.455;CD4由39.06﹪±11.03﹪升至39.21﹪±8.74﹪,t=0.093,P=0.927;CD8由28.75﹪±8.22﹪升至29.88﹪±10.13﹪,t=0.895,P=0.382;CD16+CD56+(即NK细胞)由15.73﹪±9.52﹪升至15.37﹪±6.66﹪,t=-0.173,P=0.865;EORTCQLQ-C30(vertion3.0)评分中总体健康状况(globalhealth)由(41.67±17.28)分上升至(46.43±17.19)分,P=0.076;以上各指标治疗前后差异均无统计学意义。但功能子量表中的躯体功能(physicalfunctioning)单项[由(62.94±17.48)分上升至(66.67±17.37)分,P=0.012]和症状子量表中的疲倦(fatigue)[由(51.33±20.03)分下降至(43.38±16.81)分,P=0.012]、疼痛(pain)[由44.44﹪±19.24﹪下降至(36.51±14.55)分,P=0.038]及食欲丧失(appetiteloss)[由(52.38±19.92)分下降至(38.09±21.82)分,P=0.016]单项差异均有统计学意义(P<0.05);卡氏评分由[(61.42±3.59)分上升至(62.38±4.36)分,t=1.000,P>0.05];随访1年内有3名患者死亡,生存率约85.7﹪。结论自体CIK细胞回输治疗后肿瘤标志物有明显改变,同时对缓解晚期恶性实体瘤患者的临床症状、提高其生活质量有帮助。其治疗仍有待规范和改进,远期疗效仍待观察。

Objective To observe the clinical effects of cytokine-induced killer cells （CIKs） for patients with advanced malignant solid tumor. Methods Peripheral blood mononuclear cells （PBMCs） were obtained from 50ml of peripheral blood of 21 patients. CIK cells were induced by culturing the PBMCs with cytokines and intravenously infused. Immunity indexes, levels of tumor markers, quality of life and the Karnofsky＇s score were recorded during one-year follow-up. Results Decreased levels of tumor markers were observed among 14 patients after CIK therapy 57.14 % ; flow cytometry showed that the percentage of CD3＋（from 70.81% ±10.52 % to 71.91%±11.09%, t = 0.762, P= 0.455）, CD4^＋ （from 39.06%± 11.03% to 39.21%± 8.74%, t = 0.09, P = 0.927） and CDS＋（from 28.75 % ± 8.22 % to 29.88 % ± 10.13 %, t = 0.895, P = 0.382） tended to increase （P 〉 0.05）, and that of CD16^＋CD56^＋（NK cells） （from 15.73 % ＋ 9.52 % to 15.37 % ± 6.66 %, t = -0.173, P = 0.865） decreased slightly（P 〉 0.05）;no statistical significance was observed in the average score of ＇globel health＇ （from 41.67 ±17.28 to 46.43 ± 17.19, P = 0.076）, the average score of physical functioning（from 62.94 ± 17.48 to 66.67 ＋ 17.37, P = 0.012） increased significantly. The scores of fatigue （from 51.33 ± 20.03 to 43.38 ± 16.81, P = 0.012）, pain（from 44.44 ± 19.24 to 36.51 ± 14.55, P = 0.038） and appetite loss decreased significantly （from 52.38 ± 19.92 to 38.09 ±21.82, P = 0.016）, KPS scores did not change （from 61.42 ± 3.59 to 62.38 ±4.36, t = 1.000, P 〉 0.05）.Three patients died during the follow-up and the one-year survival rate was 85.7 %. Conclusion Infusions of CIK cells are beneficial for patients with advanced malignant solid tumors. The long-term outcomes should be explored.