Dendritic cell immunotherapy combined with cytokine-induced killer cells promotes skewing toward Th2 cytokine profile in patients with metastatic non-small cell lung cancer |
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| Affiliation: | 1. Biotherapy Center, Qingdao Central Hospital, The Second Affiliated Hospital, Qingdao University Medical College, Qingdao 266042, China;2. The Affiliated Cardiovascular Hospital, Medical College of Qingdao University, Qingdao 266071, China;1. Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;2. Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;3. Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, China;4. School of Life Sciences, Zhengzhou University, Zhengzhou, China;5. State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China;2. Department of Anthropotomy and Histo-Embryology, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, China;3. Department of Spinal Surgery, Shanghai Tenth People''s Hospital, Tongji University School of Medicine, 301 Middle Yan Chang Road, Shanghai 200433, China;4. Division of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, Iowa;1. College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea;2. Korea Research Institute of Bioscience and Biotechnology, Cheongju, Chungbuk 28116, Republic of Korea |
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| 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. |
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