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Poster Presentation
Cyclic dinucleotides (CDNs) anti-tumors response by activating DC and NK cell crosstalk
  1. Juan Fu1,
  2. Drew Pardoll2 and
  3. Young J Kim1,2
  1. Aff1 grid.21107.350000000121719311Department of Otolaryngology - Head & Neck SurgeryJohns Hopkins University, School of Medicine Baltimore MD USA
  2. Aff2 grid.21107.350000000121719311Department of Oncology and the Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins University, School of Medicine Baltimore MD USA

https://doi.org/10.1186/2051-1426-2-S3-P169

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    Meeting abstracts

    Intracellular bacterial, Listeria monocytogenes generates cyclic diadenosine monophosphate (c-di-AMP) can active interferon regulatory factor3 (IRF3) and nuclear factor kappa-light-chain-enhancer (NF-κB) and induces B cell and macrophage secretion of IFN-β [1]. Cyclic diguanylic acid (c-di-GMP) also acts as an important signaling molecule in a variety of bacterial species infection functions. IFN-β actives NK cells through Tyk2-STAT1 signal pathway. Our studied showed CDNs anti-tumor effective dependent IFNα/β receptors (IFNAR1/IFNAR2) on the cell plasma membrane. Some study showed c-di-GMP significantly inhibited the proliferation of human colon cancer cells in vitro [2]. Cyclic dinucleotides (CDNs, c-di-AMP and c-di-GMP) are sensed by STING (stimulator of interferon genes). But CDNs were developed for prevent and therapeutic cancers, it was a novel method. We combined GM-CSF-producing tumor vaccine and TLR agonists enhanced systemic anti-tumor immunity. Our studied showed the regimen significantly inhibition mice tumors growth in B16 melanoma and colon cancer in vivo.

    References

    1. 1.↵
      Woodard Joshua, Iavarone Anthony T, Portnoy Daniel A: Science, Vol 328, 25 June, 2010. C-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response.
    2. 2.↵
      Steinberger O, Lapidot Z, Ben-Ishai Z, Amikam D: Elevated expression of the CD4 receptor and cell cycle arrest are induced in Jurkat cells by treatment with the novel cyclic dinucleotide 3', 5'-cyclic diguanylic acid. FEBS Lett. 444 (1999): 125-129.