原发性肝癌患者同种异体NK细胞治疗后疗效评价及外周淋巴细胞亚群变化特点  

Efficacy and peripheral immunity analysis of allogeneic natural killer cells therapy in patients with hepatocellular carcinoma

作　　者：谢云波 张纪元 杜美玲 孟繁平 福军亮 刘利敏 王松山 曲芮 廉方 乔菲 陈杨柳 高莹莹 徐若男 施明 王福生 XIE Yun-bo;ZHANG Ji-yuan;DU Mei-ling;MENG Fan-ping;FU Jun-liang;LIU Li-min;WANG Song-shan;QU Rui;LIAN Fang;QIAO Fei;CHEN Yang-liu;GAO Ying-ying;XU Ruo-nan;SHI Ming;WANG Fu-sheng(Institute of Infectious Diseases,the Fifth Medical Center of PLA General Hospital,Beijing 100039,China)

机构地区：[1]解放军总医院第五医学中心感染性疾病诊疗与研究中心

出　　处：《北京大学学报（医学版）》2019年第3期591-595,共5页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(81721002,81571567)~~

摘　　要：目的:评估同种异体自然杀伤(natural killer, NK)细胞治疗原发性肝癌的安全性和有效性,并探讨其抗肿瘤机制。方法:对21例经同种异体NK细胞治疗的原发性肝细胞癌患者进行1年随访,通过对其生存期、影像学指标、血液学指标、生物化学指标及免疫学指标分析,评价该治疗的安全性和有效性,分析患者经过治疗后外周血淋巴细胞亚群的变化。结果:(1)21例原发性肝癌患者中,11例患者治疗1次,5例患者治疗2次,5例患者治疗3次,患者治疗后未见严重不良反应,10例患者有一过性发热,1例患者出现肝区疼痛,1例患者出现头痛,未经治疗均于8 h内自行缓解;(2)在一年随访中,总疾病控制率为76.2%,其中Barcelona分期(Barcelona clinic liver cancer, BCLC)A期患者中疾病控制率为100%,病情稳定(stable disease, SD)10例;BCLC B期患者中疾病控制率为60%,部分缓解(partial response, PR)1例,SD 2例;BCLC C期患者中疾病控制率为50%,完全缓解(complete response, CR)1例,PR 2例;(3)患者治疗后24 h外周血NK细胞和CD8+T细胞频率较治疗前显著降低,CD4+T细胞频率和CD4/CD8较治疗前显著上升。结论:同种异体NK细胞治疗原发性肝细胞癌有很好的安全性和有效性。Objective: To evaluate the safety and efficacy of allogeneic natural killer (NK) cells in the treatment of primary hepatocellular carcinoma (HCC), and to elucidate the mechanism of NK cells therapy. Methods: Twenty-one patients with primary HCC treated with allogeneic NK cells at the Fifth Medical Center of the PLA General Hospital were followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donors and cultured in vitro for 15 days and infused to the patients in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, clinical features, imaging changes, hematology, immunology, and biochemical indicators to evaluate the safety and efficacy of allogeneic NK cell therapy. The changes of peripheral blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-tumor mechanisms. Results:(1) Of the 21 patients with primary HCC, 11 patients were treated once, 5 patients were treated twice, and 5 patients were treated 3 times. After allogeneic NK cells infusion, 10 patients had fever, 1 patient had slight hepatalgia and 1 patient had slight headache, no other adverse events occurred including acute and chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other treatment.(2) The total disease control rate was 76.2% during one-year follow-up. Among them, the patients with Barcelona clinic liver cancer (BCLC) stage A had a disease control rate of 100%, stable disease (SD) in 10 cases;BCLC stage B patients had a disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases;BCLC stage C patients had a disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR.(3) The frequencies of NK cells and CD8+ T cells in peripheral blood were significantly lower than that before at 24 hours after treatment, and the frequencies of CD4+ T cells and CD4/CD8 were significantly higher than the baseline. Conclusion: Allogeneic NK cells have good

关 键 词：NK细胞 肝细胞癌 同种异体 外周免疫 

分 类 号：R735.7[医药卫生—肿瘤]