目的：评价自然杀伤（natural killer, NK）细胞治疗晚期肝癌的近期临床疗效、安全性以及其对肝癌患者外周血淋巴细胞亚群和NK细胞活性的影响。方法：采集解放军307医院2013年9月至2015年9月所收治的30例晚期肝癌患者的外周血，经体外培养诱导产生NK细胞，于第14、15天进行细胞回输，连续2次回输为1疗程，共进行2个疗程治疗，分别于每疗程细胞治疗前及治疗完成2周后取患者外周血检测淋巴细胞亚群及NK细胞活性，比较治疗前、后各淋巴细胞亚群与NK细胞比例的变化，观察与临床疗效的关系。结果：30例晚期肝癌患者经NK细胞治疗后PR 4例，SD 19例，PD 7例；客观缓解率为13.3%，疾病控制率为76.7%；细胞免疫治疗前后淋巴细胞亚群无明显变化，NK细胞活性较治疗前明显提高\[（6.68±3.83）% vs （5.06±4.46）%，P<0.05\]。治疗过程中30例患者均未出现不良反应。结论：NK细胞免疫治疗可提高机体抗肝癌免疫效应，可减缓病情进展，安全性高，为晚期肝癌患者开辟一条新的治疗途径。

Objective:To observe and evaluate the clinical efficacy and safety of natural killer cells (NK) on advanced hepatocellular carcinoma (HCC), as well as its influence on the activities of lymphocyte subsets and natural killer (NK) cells in peripheral blood of HCC patients. Methods: We collected peripheral blood (PB) from 30 patients with advanced hepatocellular carcinoma from September 2013 to September 2015 at No. 307 Hospital of PLA. The NK cells were generated through cultivation and induction in vitro, and were re-transfused into patients at the 14th and the 15th day. Two consecutive transfusions were regarded as one cycle, and there were totally two cycles. We detected the activities of lymphocyte subsets and NK cells in peripheral blood at pre-treatment and 2 weeks post-treatment for each cycle, respectively, and observed the activity changes of the lymphocyte subsets and NK cells before and after the treatment as well as its relationship to clinical efficacy. Results: Among the 30 HCC patients, there were 4 cases of PR, 19 cases of SD and 7 cases of PD after NK treatment; the objective response rate and disease control rate were 13.3% and 76.7 % respectively. The lymphocyte subsets didn't show obvious change, but the NK cell activity increased significantly after the treatment (\[5.06±4.46\]% vs \[6.68±3.83\] %, P<0.05). None of the 30 patients had adverse effects. Conclusion:The NK cell immunotherapy can improve the anti-tumor and immunity effect of body and slow-down the disease progression; it is a new and safe treatment approach for HCC patients.

国家科技重大专项“十二五”计划基金资助项目（No.2009zx09503）