Zhao Yan-Jie, Jiang Ni, Song Qing-Kun, Wu Jiang-Ping, Song Yu-Guang, Zhang Hong-Mei, Chen Feng, Zhou Lei, Wang Xiao-Li, Zhou Xin-Na, Yang Hua-Bing, Ren Jun, Lyerly Herbert Kim
Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines, Beijing, China E-mail :
Asian Pac J Cancer Prev. 2015;16(6):2419-23. doi: 10.7314/apjcp.2015.16.6.2419.
There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients.
A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits.
An average of 5.7±2.94x10(9) induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic CD8+CD28+T lymphocytes were increased by 74% and suppressive CD8+CD28-T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of CD8+CD28- T cell proportion reflecting a 5% higher risk of progression (p<0.05).
In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.
对于那些对传统抗癌治疗无反应或不耐受的晚期癌症患者，治疗选择有限。因此，本研究旨在探讨持续输注树突状细胞-细胞因子诱导的杀伤细胞在此类患者中的益处和临床疗效。
本研究共纳入381次输注（来自67例招募的晚期病例）。所有患者均接受外周血单个核细胞采集以进行后续细胞治疗，并在体外扩增树突状细胞-细胞因子诱导的杀伤细胞。通过流式细胞术对外周血T淋巴细胞亚群进行定量分析，以评估细胞免疫状态。分别采用实体瘤疗效评价标准（RECIST）和东部肿瘤协作组（ECOG）评分评估临床疗效和身体活动情况。采用逻辑回归模型估计细胞输注与临床获益之间的关联。
每次平均输注5.7±2.94×10⁹个诱导细胞，患者接受6次输注。细胞免疫得到改善，细胞毒性CD8⁺CD28⁺T淋巴细胞增加74%，抑制性CD8⁺CD28⁻T淋巴细胞升高16%（p<0.05）。持续输注树突状细胞-细胞因子诱导的杀伤细胞与患者状态和细胞免疫的改善相关。中位6次输注能够将疾病进展风险降低70%（95%CI 0.10 - 0.91）。ECOG评分每升高1分，疾病进展风险相应增加3.90倍（p<0.05），CD8⁺CD28⁻T细胞比例每增加1%，疾病进展风险相应增加5%（p<0.05）。
在晚期癌症患者中，持续输注树突状细胞-细胞因子诱导的杀伤细胞能够恢复细胞免疫，改善对传统癌症治疗无反应患者的状态和生活质量。
