A novel dendritic cell subset involved in tumor immunosurveillance

NATURE MEDICINE 12, 214-219, 2006

Speaker: 賴柏吟                                       Time: 2006/4/19 13:10 ~ 14:00

Commentator: Dr.黎煥耀                             Place: Room 601

Abstract:

IFN-g plays an important role in immune surveillance to against tumor progression via up-regulating antigen processing and the presentation on tumor cells. The primary source of IFN-gproduction in tumor-bearing animals is still unclear to day. In the seminar paper, the authors tried to demonstrate that the IFN-g secreting cells infiltrating in tumor site mediate the anti-tumor effect. After treatment of the anti-cancer drug imatinib mesylate (also called Gleevec), tumor cells were lysed by tumor infiltrated DCs that secreted high levels of IFN-g. In addition, combined treatment of Gleevec plus IL-2 induced prominent CD11c⁺ cells infiltrating in tumor and enhanced the anti-tumor effect of NK-like cells. The CD11c⁺/NK1.1⁺ cells infiltrating in tumor may be cells of DCs and NK cells, as they both express CD11c⁺ marker. To further differentiate the cell origin the authors isolated tumor infiltrating CD11c⁺ cells of Gleevec- and IL-2-treated mice for surface marker characterization by flow cytometric analysis. They found that the tumor infiltrating B220⁺/NK1.1⁺ cells can be classified as a new subset of DCs and termed interferon-producing killer dendritic cells or IKDCs. These cells can produce high level of IFN-g and effectively kill tumor cells through a TRAIL-dependent pathway under Gleevec + IL-2 treatment. Furthermore, only IKDCs, but not conventional DCs or NK cells, were effective and sufficient to prevent tumor outgrowth in vivo suggesting a unique role of IKDCs in tumor immunosurveillance.

References:

1.        Borg, C. et al. Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects. J. Clin. Invest. 114, 379–388, 2004.

2.        Taieb, J. et al. A novel dendritic cell subset involved in tumor immunosurveillance. NAT. MED. 12, 214-219, 2006.