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治疗周期数和间隔对细胞因子诱导的杀伤细胞及其在晚期非小细胞肺癌(NSCLC)中的辅助治疗效果的影响。

Influence of the number and interval of treatment cycles on cytokine-induced killer cells and their adjuvant therapeutic effects in advanced non-small-cell lung cancer (NSCLC).

作者信息

Gu Yuanlong, Lv Huimin, Zhao Juan, Li Qi, Mu Guannan, Li Jiade, Wuyang Jiazi, Lou Ge, Wang Ruitao, Zhang Yanqiao, Huang Xiaoyi

机构信息

Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China.

Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin 150081, China.

出版信息

Int Immunopharmacol. 2017 Sep;50:263-269. doi: 10.1016/j.intimp.2017.07.006. Epub 2017 Jul 12.

DOI:10.1016/j.intimp.2017.07.006
PMID:28711032
Abstract

OBJECTIVE

Cytokine-induced killer (CIK) cells have important therapeutic effects in adoptive cell transfer (ACT) for the treatment of various malignancies. In this study, we focused on in vitro expansion of CIK cells and their clinical efficacy in combination with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).

METHODS

A total of 64 patients with NSCLC (enrolled from 2011 to 2012), including 32 patients who received chemotherapy alone or with sequential radiotherapy (conventional treatment, control group) and 32 patients who received conventional treatment and sequential CIK infusion (study group), were retrospectively analyzed. The time to progression (TTP), overall survival (OS) and adverse effects were analyzed and the phenotype of lymphocytes in CIK population was also determined by flow cytometry.

RESULTS

After in vitro expansion, the average percentage of CIK cells was 26.35%. During the 54-month follow up, the median OS and TTP were significantly longer in the study group than in the control group (P=0.0189 and P=0.0129, respectively). The median OS of the ACT≥4cycles subgroup was significantly longer than that of the ACT<4cycles subgroup (P=0.0316). The percentage of CIK cells in patients who received ≥4cycles of ACT was higher than that in patients treated with <4cycles of ACT (P=0.0376). Notably, CIK cells were difficult to expand in vitro in some patients after the first ACT cycle but became much easier as the treatment cycles increased monthly. Longer treatment interval negatively impacted the expansion of CIK cells.

CONCLUSIONS

Systematic immune levels can be increasingly boosted by reinfusion of ACT. Conventional treatment plus CIK cells is an effective therapeutic strategy to prevent progression and prolong survival of patients with advanced NSCLC.

摘要

目的

细胞因子诱导的杀伤(CIK)细胞在过继性细胞转移(ACT)治疗各种恶性肿瘤中具有重要的治疗作用。在本研究中,我们重点关注CIK细胞的体外扩增及其联合化疗在晚期非小细胞肺癌(NSCLC)患者中的临床疗效。

方法

回顾性分析了2011年至2012年纳入的64例NSCLC患者,其中32例接受单纯化疗或序贯放疗(传统治疗,对照组),32例接受传统治疗并序贯CIK输注(研究组)。分析疾病进展时间(TTP)、总生存期(OS)和不良反应,并通过流式细胞术测定CIK群体中淋巴细胞的表型。

结果

体外扩增后,CIK细胞的平均百分比为26.35%。在54个月的随访期间,研究组的中位OS和TTP显著长于对照组(分别为P = 0.0189和P = 0.0129)。ACT≥4周期亚组的中位OS显著长于ACT<4周期亚组(P = 0.0316)。接受≥4周期ACT的患者中CIK细胞的百分比高于接受<4周期ACT治疗的患者(P = 0.0376)。值得注意的是,在一些患者中,首次ACT周期后CIK细胞在体外难以扩增,但随着每月治疗周期的增加变得容易得多。较长的治疗间隔对CIK细胞的扩增有负面影响。

结论

ACT再输注可逐渐提高系统免疫水平。传统治疗加CIK细胞是预防晚期NSCLC患者病情进展和延长生存期的有效治疗策略。

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