目的：评价肿瘤特异性个体化多靶点树突状细胞-细胞因子诱导的杀伤细胞（DC-CIK）治疗晚期非小细胞肺癌（NSCLC）患者的临床疗效和安全性。方法：回顾性分析2019 年10 月1日至2022 年10 月31 日东部战区总医院生物治疗科行肿瘤特异性个体化多靶点DC-CIK 治疗晚期NSCLC患者的临床资料。统计NSCLC患者的临床疗效和不良反应，分析治疗前后血清中肿瘤标志物的变化，FCM检测患者治疗前后的淋巴细胞亚群和各种细胞因子的表达情况，用质谱仪检测治疗前后靶点的变化。结果:共入组52 例晚期NSCLC 患者，其中女性21例、男性31例；年龄32~71岁，平均年龄（50.97±10.72）岁，中位年龄47.5岁。经DC-CIK 治疗后，CR 0例，PR 0例，SD 27 例，PD 25 例。与治疗前比较，DC-CIK 治疗后：（1）CEA和CYFRA21-1水平无显著改变，CA125 水平显著低于治疗前（P<0.01）；（2）治疗后患者淋巴细胞亚群无显著变化；（3）治疗后患者外周血IL-2、IL-4、IFN-γ 和TNF-α水平显著升高（均P<0.01），IL-6、IL-10 及IL-17 水平无明显变化（；4）治疗后靶点数下降明显。DC-CIK 治疗过程中无严重不良反应发生。结论:晚期NSCLC患者行肿瘤特异性个体化多靶点自体DC-CIK 治疗是安全的，能使患者产生抗肿瘤免疫反应并得到一定的临床获益。

Objective: To evaluate the clinical efficacy and safety of tumor-specific individualized multi-target dendritic cell-cytokine-induced killer cell (DC-CIK) in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Methods: The clinical data of patients with advanced NSCLC who underwent tumor-specific individualized multi-target DC-CIK therapy in the Biotherapy Department of the Eastern Theater General Hospital from October 1, 2019 to October 31, 2022 were retrospectively analyzed. The clinical data and adverse reactions of NSCLC patients were collected. The short-term clinical efficacy was evaluated by the changes of tumor markers in serum before and after the DC-CIK treatment, and the expression of lymphocyte subsets and various cytokines in patients before and after the treatment was detected by flow cytometry. Mass spectrometry was used to detect the changes in the number of targets before and after the treatment. Results: A total of 52 patients with advanced NSCLC were enrolled, including 21 females and 31 males; the age ranged from 32 to 71, with an average age of (50.97±10.72) years old and a median age of 47.5 years old. After DC-CIK treatment, there were 0 cases of CR, 0 cases of PR, 27 cases of SD and 25 cases of PD. Compared with pre-treatment, (1) there was no significant difference in the levels of CEA and CYFRA21-1 after treatment, but the level of CA125 was significantly decreased (P<0.01); (2) there was no significant change in the lymphocyte subsets of patients after treatment; (3) the levels of IL-2, IL-4, IFN-γ, and TNF-α in the peripheral blood of patients were significantly increased (all P<0.01), while the levels of IL-6, IL-10, and IL-17 did not change significantly; (4) the number of targets decreased significantly after treatment. There was no serious adverse reactions occurred during the DC-CIK treatment. Conclusion: Tumor-specific individualized multi-target autologous DC-CIK therapy is safe for patients with advanced NSCLC and can induce anti-tumor immune response in patients, thus bringing clinical benefits.

2022东部战区总医院院管课题（No. 22JCYYYB1）