title: Dendritic cell immunotherapy combined with cytokine-induced killer cells promotes skewing toward Th2 cytokine profile in patients with metastatic non-small cell lung cancer.
abstract: Dendritic cell (DC) vaccination and cytokine-induced killer (CIK) cell therapy (DC/CIK) have shown limited success in the treatment of advanced non-small cell lung cancer (NSCLC). To investigate the reason for this limited success, the effects of DC/CIK cell therapy on the immune responses of tumor-bearing patients and patients with resected NSCLC were evaluated. In the total 50 patients studied, the serum concentrations of the Th2 cytokines (IL-4 and IL-10) in tumor-bearing patients were significantly higher than those with resected NSCLC before immunotherapy. The post-therapy Th1 cytokine (IFN-γ) level in patients with resected NSCLC significantly increased from the pre-therapy level. In contrast, significantly enhanced post-therapy Th2 cytokine (IL-4 and IL-10) levels were found in tumor-bearing patients. The intracellular staining assay revealed that DC/CIK cell therapy increased the IFN-γ-producing T lymphocyte (CD8(+)IFN-γ(+)) frequency in patients with resected NSCLC, but these lymphocytes were not found in tumor-bearing patients. Furthermore, overproduction of vascular endothelial growth factor (VEGF) in tumor-bearing patients showed a statistically positive correlation with IL-4, suggesting that VEGF might be responsible for the predominance of serum Th2 cytokines. In a word, tumor-bearing patients developed a Th2-dominant status that could not be reversed toward Th1 following immunotherapy. A combined regiment of DC vaccination and CIK cell therapy with other treatments to overcome systemic Th2-dominant immune response might improve the current clinical benefit.
authors.affiliation: Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao 266042, China. Electronic address: zp8102@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: The Affiliated Cardiovascular Hospital, Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Bu
authors.affiliation: Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao 266042, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wei
authors.affiliation: Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao 266042, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Sun
authors.affiliation: Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao 266042, China.
authors.forename: Xihe
authors.initials: X
authors.lastname: Xie
authors.affiliation: Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao 266042, China.
authors.forename: Changyou
authors.initials: C
authors.lastname: Li
authors.affiliation: Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao 266042, China.
authors.forename: Qingming
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao 266042, China.
authors.forename: Danni
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao 266042, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Wei
authors.affiliation: Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao 266042, China. Electronic address: daiqinggao@126.com.
authors.forename: Daiqing
authors.initials: D
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000276:immunology / Q000628:therapy*; D055612:Cytokine-Induced Killer Cells / Q000637:transplantation*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D015847:Interleukin-4 / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018418:Th2 Cells / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D016207:Cytokines; C508598:IL4 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4
keywords: CIK cells; Dendritic cells; Immune response; Immunotherapy; Non-small cell lung cancer