TNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors.
<h4>Background</h4>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 i...
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2012
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oai:doaj.org-article:94d30197e043423da1dc5e15ecefd5202021-11-18T08:03:50ZTNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors.1932-620310.1371/journal.pone.0052926https://doaj.org/article/94d30197e043423da1dc5e15ecefd5202012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300824/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods</h4>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-γ and serum IL-12 were measured in order to determine the immune response following the DC-based immunotherapy.<h4>Results</h4>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.<h4>Conclusions</h4>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.Shinji MiwaHideji NishidaYoshikazu TanzawaMunetomo TakataAkihiko TakeuchiNorio YamamotoToshiharu ShiraiKatsuhiro HayashiHiroaki KimuraKentaro IgarashiEishiro MizukoshiYasunari NakamotoShuichi KanekoHiroyuki TsuchiyaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e52926 (2012) |
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DOAJ |
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Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Shinji Miwa Hideji Nishida Yoshikazu Tanzawa Munetomo Takata Akihiko Takeuchi Norio Yamamoto Toshiharu Shirai Katsuhiro Hayashi Hiroaki Kimura Kentaro Igarashi Eishiro Mizukoshi Yasunari Nakamoto Shuichi Kaneko Hiroyuki Tsuchiya TNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors. |
| description |
<h4>Background</h4>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.<h4>Methods</h4>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-γ and serum IL-12 were measured in order to determine the immune response following the DC-based immunotherapy.<h4>Results</h4>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.<h4>Conclusions</h4>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. |
| format |
article |
| author |
Shinji Miwa Hideji Nishida Yoshikazu Tanzawa Munetomo Takata Akihiko Takeuchi Norio Yamamoto Toshiharu Shirai Katsuhiro Hayashi Hiroaki Kimura Kentaro Igarashi Eishiro Mizukoshi Yasunari Nakamoto Shuichi Kaneko Hiroyuki Tsuchiya |
| author_facet |
Shinji Miwa Hideji Nishida Yoshikazu Tanzawa Munetomo Takata Akihiko Takeuchi Norio Yamamoto Toshiharu Shirai Katsuhiro Hayashi Hiroaki Kimura Kentaro Igarashi Eishiro Mizukoshi Yasunari Nakamoto Shuichi Kaneko Hiroyuki Tsuchiya |
| author_sort |
Shinji Miwa |
| title |
TNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors. |
| title_short |
TNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors. |
| title_full |
TNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors. |
| title_fullStr |
TNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors. |
| title_full_unstemmed |
TNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors. |
| title_sort |
tnf-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/94d30197e043423da1dc5e15ecefd520 |
| work_keys_str_mv |
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| _version_ |
1718422300767813632 |