PLoS ONE (Jan 2012)

TNF-α and tumor lysate promote the maturation of dendritic cells for immunotherapy for advanced malignant bone and soft tissue tumors.

  • 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

DOI
https://doi.org/10.1371/journal.pone.0052926
Journal volume & issue
Vol. 7, no. 12
p. e52926

Abstract

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BackgroundDendritic 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.MethodsThirty-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.ResultsApproximately 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.ConclusionsAlthough 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.