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CIK细胞免疫疗法联合化疗治疗非小细胞肺癌的临床疗效
引用本文:马晓骉,罗峰,高永亮,郝静超. CIK细胞免疫疗法联合化疗治疗非小细胞肺癌的临床疗效[J]. 昆明医科大学学报, 2020, 41(12): 60-67. DOI: 10.12259/j.issn.2095-610X.S20201215
作者姓名:马晓骉  罗峰  高永亮  郝静超
作者单位:1.云南省肿瘤医院/昆明医科大学第三附属医院肿瘤生物治疗中心,云南 昆明  650118
基金项目:云南省科技厅-昆明医科大学应用基础研究联合专项;云南省教育厅科研项目
摘    要:  目的  评价化疗联合CIK(cytokine-induced killer)细胞免疫疗法对非小细胞肺癌NSCLC早期、晚期患者的临床疗效。  方法  收集2013年1月至2016年12月昆明医科大学第三附属医院收治NSCLC患者122例为研究对象,按患者病程分为Ⅰ-Ⅱ期和Ⅲ-Ⅳ期,将其随机分入4个受试组:化疗A组(n = 30),联合CIK A组(n = 31),化疗B组(n = 30),联合CIK B组(n = 31)。其中,受试组采用化疗方法均为吉西他滨联合顺铂治疗(GP)。评价患者临床疗效、生存质量和外周血淋巴细胞和细胞因子变化。  结果  与化疗组比较,联合CIK治疗组显著提高ORR值和DCR值,分别是(67.74%,45.16%)和(74.19%,64.52%)(P < 0.05);提高KPS评分和ECOG评分,分别是(80.65%,58.06%)和(80.65%,70.97%)( P < 0.05);提高患者外周血中CD3 +、CD8+淋巴细胞亚群比率及CIK细胞比率(P < 0.05);提高患者外周血中IFN-γ,TNF-α、IL-4、IL-6细胞因子表达水平( P < 0.05);延长患者生存期( P < 0.05)。与联合CIK A组(Ⅰ-Ⅱ期)比较,联合CIK B组(Ⅲ-Ⅳ期)患者外周血中CD3 +、CD4+、CD8+、CD4+/CD8+T淋巴细胞亚群、NK细胞比率、CIK细胞比率均显著提高(P < 0.05),维持和调控增强外周血中IFN-γ,TNF-α、IL-2、IL-4、IL-6细胞因子表达水平( P < 0.05)。  结论  化疗联合CIK细胞治疗能显著提高不同阶段NSCLC患者临床疗效、延长生存期、提高近期生存质量,提高化疗期患者体内免疫细胞持续对抗肿瘤的细胞毒性和免疫应答能力,尤其对晚期患者的疗效更佳。

关 键 词:CIK细胞免疫治疗   非小细胞肺癌   化学治疗   联合治疗
收稿时间:2020-04-16

Clinical Study of Chemotherapy Combined with CIK Cell Immunotherapy for Non-small Cell Lung Cancer
Affiliation:1.Yunnan Cancer Hospital,The 3rd Affiliated Hospital of Kunming Medical University,Kunming Yunnan 6501182.School of Pharmaceutical Science,Key Laboratory of Natural Pharmacology of Yunnan Province,Kunming Medical University, Kunming Yunnan 650500,China
Abstract:  Objective  To evaluate the clinical efficacy of chemotherapy combined with CIK (cytokine-induced killer)cell immunotherapy on early and advanced stages non small cell lung cancer (NSCLC)patients.  Methods  A total of 122 NSCLC patients admitted to the Third Affiliated Hospital of Kunming Medical University from 2013 to 2016, according to the course of disease, the patients divided into early stage (stage I-II)and late stage (stage III-IV); and were randomly divided into four groups: chemotherapy a group (n = 30), combined with CIK a group (n = 31), chemotherapy B group (n = 30), combined with CIK B group (n = 31). Among them, gemcitabine combined with cisplatin (GP)was used in all the groups. The clinical efficacy, quality of life and changes of peripheral blood lymphocytes and cytokines were evaluated.  Results  Compared with the chemotherapy group, the ORR and DCR values were significantly increased (67.74%, 45.16%)and (74.19%, 64.52%)respectively (P < 0.05), KPS and ECOG scores were significantly increased (80.65%, 58.06%)and (80.65%, 70.97%) respectively ( P < 0.05), in the combined CIK groups. The ratio of CD3 +, CD8+ lymphocytes and CIK cells in patients' peripheral blood was significantly increased (P < 0.05)and the expression level of IFN - γ, TNF - α, IL-4 and IL-6 cytokines in patients' peripheral blood was significantly increased ( P < 0.05)and the survival period of patients was prolonged ( P < 0.05)in the combined CIK groups. Compared with the combined CIK A group (early stage), the ratio of CD3 +, CD4+, CD8+, CD4+/CD8+ T lymphocytes, NK cell ratio and CIK cell ratio in the peripheral blood of the patients were significantly increased, and the expression levels of IFN - γ, TNF - α, IL-2, IL-4 and IL-6 cytokines in the peripheral blood were maintained and enhanced in the combined CIK B group (advanced stage)(P < 0.05).  Conclusion  Chemotherapy combined with CIK cell therapy can significantly improve the clinical efficacy, prolong the survival period, and improve the short-term quality of life of NSCLC patients in different stages, and significantly improve the ability of immune cells in vivo to continuously resist tumor cytotoxicity and immune response, especially for patients in advanced stage.
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