Augmentation of autologous T cell reactivity with acute myeloid leukemia (AML) blasts by Toll-like receptor (TLR) agonists

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• 作者：RuiKun Zhong ; Hongying Li ; Karen Messer ; Thomas A. Lane…
• 关键词：Acute myeloid leukemia ; Dendritic cells ; Toll ; like receptor ; Cytotoxic T lymphocytes ; Resiquimod ; Lipopolysaccharide
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：64
• 期：6
• 页码：737-744
• 全文大小：733 KB
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• 作者单位：RuiKun Zhong (1)
  Hongying Li (1)
  Karen Messer (1)
  Thomas A. Lane (1)
  Jiehua Zhou (1)
  Edward D. Ball (1)
  
  1. Division of Blood and Marrow Transplantation, Departments of Medicine, Pathology and the Moores UCSD Cancer Center, University of California, San Diego, 3855 Health Sciences Drive, La Jolla, CA, 92093-0960, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851

文摘

This study investigated whether TNF-α, Toll-like receptors (TLRs) 7/8 agonist resiquimod (R848), the TLR4 agonist lipopolysaccharide (LPS) and their combinations can enhance autologous AML-reactive T cell generation in an in vitro culture. AML peripheral blood or bone marrow mononuclear cells were cultured in medium supplemented with GM-CSF/IL-4 to induce dendritic cell (DC) differentiation of AML blasts (AML-DC). The impact of TNF-α, LPS, R848 and their combinations on AML-DC cultures was analyzed. Significantly enhanced CD80, CD40, CD83, CD54, HLA-DR and CD86 expression of AML cells was observed by addition of TNF-α, LPS, R848 alone or combinations. Induced CD80 expression of AML cells was significantly higher through the combination of TNF-α, LPS and R848 (T?+?L?+?R) than that by T alone. CTL induced from T?+?L?+?R, T?+?R, T?+?L, L?+?R and R, but not T, L alone stimulated cultures showed significantly higher IFN-γ release than the medium control in response to autologous AML cells. IFN-γ release by T?+?L?+?R was significantly higher than T or L alone, and T?+?R was significantly higher than T alone. CTL generated from T?+?L?+?R, T?+?L, T?+?R, L?+?R and L alone exerted significantly higher AML cell killing than medium control. AML cell killing by T?+?L?+?R and T?+?R was significantly higher than T or R alone. These results indicate that the combination of T?+?L?+?R induces a significantly enhanced antigen presentation effect of AML-DC. We speculate that the complementary effects of reagent combinations may better address the heterogeneity of responses to any single agent in AML cells from different patients.