Lin Mao, Liang Shuzhen, Wang Xiaohua, Liang Yinqing, Zhang Mingjie, Chen Jibing, Niu Lizhi, Xu Kecheng
Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, China.
Fuda Cancer Institute, Guangzhou, China.
Oncotarget. 2017 May 11;8(47):81967-81977. doi: 10.18632/oncotarget.17804. eCollection 2017 Oct 10.
In this study, the clinical efficacy of cryosurgery combined with allogenic natural killer cell immunotherapy for advanced hepatocellular cancer was evaluated. From October 2015 to March 2017, we enrolled 61 patients who met the enrollment criteria and divided them into two groups: 1) the simple cryoablation group (Cryo group, = 26); and 2) the cryoablation combined with allogenic natural killer cells group (Cryo-NK group, = 35), the safety and short-term effects were evaluated firstly, then the median progression-free survival, response rate and disease control rate were assessed. All adverse events experienced by the patients were recorded, and included local (e.g., pain, pleural effusion, and ascites) and systemic (e.g., chills, fatigue, and fever) reactions, fever was more frequent. Other possible seriously side effects (e.g., blood or bone marrow changes) were not detected. Combining allogeneic natural killer cells with cryoablation had a synergistic effect, not only enhancing the immune function, improving the quality of life of the patients, but also reducing the expression of AFP and significantly exhibiting good clinical efficacy of the patients. After a median follow-up of 8.7 months (3.9 -15.1months), median progression-free survival was higher in Cryo-NK (9.1 months) than in Cryo (7.6 months, = 0.0107), median progression-free survival who received multiple natural killer was higher than who just received single natural killer (9.7 months vs.8.4 months, = 0.0011, respectively), the response rate in Cryo-NK (60.0%) was higher than in Cryo (46.1%, < 0.05), the disease control rate in Cryo-NK (85.7%) was higher than in Cryo group (69.2%, < 0.01). Percutaneous cryoablation combined with allogeneic natural killer cell immunotherapy significantly increased median progression-free survival of advanced hepatocellular cancer patients. Multiple allogeneic natural killer cells infusion was associated with better prognosis to advanced hepatocellular cancer.
本研究评估了冷冻消融联合异基因自然杀伤细胞免疫疗法治疗晚期肝细胞癌的临床疗效。2015年10月至2017年3月，我们纳入了61例符合纳入标准的患者，并将他们分为两组：1）单纯冷冻消融组（冷冻组，n = 26）；2）冷冻消融联合异基因自然杀伤细胞组（冷冻 - NK组，n = 35），首先评估安全性和短期疗效，然后评估中位无进展生存期、缓解率和疾病控制率。记录患者经历的所有不良事件，包括局部（如疼痛、胸腔积液和腹水）和全身（如寒战、疲劳和发热）反应，发热较为常见。未检测到其他可能的严重副作用（如血液或骨髓变化）。将异基因自然杀伤细胞与冷冻消融相结合具有协同作用，不仅增强免疫功能、改善患者生活质量，还降低甲胎蛋白表达，显著展现出良好的临床疗效。中位随访8.7个月（3.9 - 15.1个月）后，冷冻 - NK组的中位无进展生存期（9.1个月）高于冷冻组（7.6个月，P = 0.0107），接受多次自然杀伤细胞治疗的患者中位无进展生存期高于仅接受单次自然杀伤细胞治疗的患者（分别为9.7个月对8.4个月，P = 0.0011），冷冻 - NK组的缓解率（60.0%）高于冷冻组（46.1%，P < 0.05），冷冻 - NK组的疾病控制率（85.7%）高于冷冻组（69.2%，P < 0.01）。经皮冷冻消融联合异基因自然杀伤细胞免疫疗法显著提高了晚期肝细胞癌患者的中位无进展生存期。多次输注异基因自然杀伤细胞与晚期肝细胞癌更好的预后相关。
