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- Title
TNF-α and Tumor Lysate Promote the Maturation of Dendritic Cells for Immunotherapy for Advanced Malignant Bone and Soft Tissue Tumors.
- Authors
Miwa, Shinji; Nishida, Hideji; Tanzawa, Yoshikazu; Takata, Munetomo; Takeuchi, Akihiko; Yamamoto, Norio; Shirai, Toshiharu; Hayashi, Katsuhiro; Kimura, Hiroaki; Igarashi, Kentaro; Mizukoshi, Eishiro; Nakamoto, Yasunari; Kaneko, Shuichi; Tsuchiya, Hiroyuki
- Abstract
Background: Dendritic cells (DCs) play a pivotal role in the immune system. There are many reports concerning DC-based immunotherapy. The differentiation and maturation of DCs is a critical part of DC-based immunotherapy. We investigated the differentiation and maturation of DCs in response to various stimuli. Methods: Thirty-one patients with malignant bone and soft tissue tumors were enrolled in this study. All the patients had metastatic tumors and/or recurrent tumors. Peripheral blood mononuclear cells (PBMCs) were suspended in media containing interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF). These cells were then treated with or without 1) tumor lysate (TL), 2) TL + TNF-α, 3) OK-432. The generated DCs were mixed and injected in the inguinal or axillary region. Treatment courses were performed every week and repeated 6 times. A portion of the cells were analyzed by flow cytometry to determine the degree of differentiation and maturation of the DCs. Serum IFN-c and serum IL-12 were measured in order to determine the immune response following the DC-based immunotherapy. Results: Approximately 50% of PBMCs differentiated into DCs. Maturation of the lysate-pulsed DCs was slightly increased. Maturation of the TL/TNF-α-pulsed DCs was increased, commensurate with OK-432-pulsed DCs. Serum IFN-γ and serum IL- 12 showed significant elevation at one and three months after DC-based immunotherapy. Conclusions: Although TL-pulsed DCs exhibit tumor specific immunity, TL-pulsed cells showed low levels of maturation. Conversely, the TL/TNF-α-pulsed DCs showed remarkable maturation. The combination of IL-4/GM-CSF/TL/TNF-α resulted in the greatest differentiation and maturation for DC-based immunotherapy for patients with bone and soft tissue tumors.
- Subjects
DENDRITIC cells; IMMUNE system; IMMUNOTHERAPY; CELL differentiation; SOFT tissue tumors
- Publication
PLoS ONE, 2012, Vol 7, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0052926