Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy with Cytokine-Induced Killer Cells Improves Survival in Gastric and Colorectal Cancer Patients

作者: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
来源:PLos One, 2014, 9(4): e93886.
DOI:10.1371/journal.pone.0093886

摘要

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-gamma, 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 +/- 79.8x10(6) DCs and 58.8 +/- 22.3x10(8) CIK cells. Cytokine levels in patients%26apos; 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-gamma 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%26lt;0.01) with an increased OS (%26lt;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.