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自体肿瘤裂解物脉冲树突状细胞联合细胞因子诱导的杀伤细胞免疫疗法可提高胃癌和结直肠癌患者的生存率。

Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients.

作者信息

Gao Daiqing, Li Changyou, Xie Xihe, Zhao Peng, Wei Xiaofang, Sun Weihong, Liu Hsin-Chen, Alexandrou Aris T, Jones Jennifer, Zhao Ronghua, Li Jian Jian

机构信息

Biotherapy Center, Qingdao Center Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao, China.

Department of Radiation Oncology, NCI-Designated Comprehensive Cancer Center, University of California at Davis Sacramento, Sacramento, California, United States of America.

出版信息

PLoS One. 2014 Apr 3;9(4):e93886. doi: 10.1371/journal.pone.0093886. eCollection 2014.

Abstract

Gastric and colorectal cancers (GC and CRC) have poor prognosis and are resistant to chemo- and/or radiotherapy. In the present study, the prophylactic effects of dendritic cell (DC) vaccination are evaluated on disease progression and clinical benefits in a group of 54 GC and CRC patients treated with DC immunotherapy combined with cytokine-induced killer (CIK) cells after surgery with or without chemo-radiotherapy. DCs were prepared from the mononuclear cells isolated from patients using IL-2/GM-CSF and loaded with tumor antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. The DC/CIK therapy started 3 days after low-dose chemotherapy and was repeated 3-5 times in 2 weeks as one cycle with a total of 188.3 ± 79.8 × 10(6) DCs and 58.8 ± 22.3 × 10(8) CIK cells. Cytokine levels in patients' sera before and after treatments were measured and the follow-up was conducted for 98 months to determine disease-free survival (DFS) and overall survival (OS). The results demonstrate that all cytokines tested were elevated with significantly higher levels of IFN-γ and IL-12 in both GC and CRC cohorts of DC/CIK treated patients. By Cox regression analysis, DC/CIK therapy reduced the risk of post-operative disease progression (p<0.01) with an increased OS (<0.01). These results demonstrate that in addition to chemo- and/or radiotherapy, DC/CIK immunotherapy is a potential effective approach in the control of tumor growth for post-operative GC and CRC patients.

摘要

胃癌和结直肠癌(GC和CRC)预后较差,且对化疗和/或放疗具有抗性。在本研究中,对54例接受DC免疫疗法联合细胞因子诱导的杀伤细胞(CIK)治疗的GC和CRC患者进行评估,观察树突状细胞(DC)疫苗接种对疾病进展和临床益处的预防作用,这些患者术后接受或未接受放化疗。DC由使用IL-2/GM-CSF从患者分离的单核细胞制备,并负载肿瘤抗原;CIK细胞通过将外周血淋巴细胞与IL-2、IFN-γ和CD3抗体孵育制备。DC/CIK治疗在低剂量化疗后3天开始,在2周内重复3 - 5次作为一个周期,共使用188.3±79.8×10(6)个DC和58.8±22.3×10(8)个CIK细胞。测量患者治疗前后血清中的细胞因子水平,并进行98个月的随访以确定无病生存期(DFS)和总生存期(OS)。结果表明,所有检测的细胞因子均升高,在接受DC/CIK治疗的GC和CRC队列患者中,IFN-γ和IL-12水平显著更高。通过Cox回归分析,DC/CIK治疗降低了术后疾病进展的风险(p<0.01),OS增加(<0.01)。这些结果表明,除了化疗和/或放疗外,DC/CIK免疫疗法是控制术后GC和CRC患者肿瘤生长的一种潜在有效方法。

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