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题名:Serial killing of tumor cells by human natural killer cells - enhancement by therapeutic antibodies.
作者:Bhat R, Watzl C. Related Articles, Links
来源:PLoS ONE[IF=----]. 2007 Mar 28;2:e326.
URL :1http://dx.doi.org/0.1371/journal.pone.0000326
日期:070415
摘要: Rauf Bhat and Carsten Watzl*

Institute for Immunology, University Heidelberg, Heidelberg, Germany

Centre de Recherche Public-Sant, Luxembourg

* To whom correspondence should be addressed. E-mail: Carsten.watzl@urz.uni-heidelberg.de
Conceived and designed the experiments: CW. Performed the experiments: RB. Analyzed the data: CW RB. Wrote the paper: CW RB.

Received February 22, 2007; Accepted February 26, 2007.

Abstract

Background
Natural killer cells are an important component of the innate immune system. Anti-cancer therapies utilizing monoclonal antibodies also rely on the cytotoxicity of NK cells for their effectiveness. Here, we study the dynamics of NK cell cytotoxicity.

Methodology/Principal Findings
We observe that IL-2 activated human NK cells can serially hit multiple targets. Using functional assays, we demonstrate that on an average, a single IL-2 activated NK cell can kill four target cells. Data using live video microscopy suggest that an individual NK cell can make serial contacts with multiple targets and majority of contacts lead to lysis of target cells. Serial killing is associated with a loss of Perforin and Granzyme B content. A large majority of NK cells survive serial killing, and IL-2 can replenish their granular stock and restore the diminished cytotoxicity of exhausted NK cells. IL-2 and IL-15 are equally effective in enhancing the killing frequency of resting NK cells. Significantly, Rituximab, a therapeutic monoclonal antibody increases the killing frequency of both resting and IL-2 activated NK cells.

Conclusion/Significance
Our data suggest that NK cell-based therapies for overcoming tumors rely on their serial killing ability. Therefore, strategies augmenting the killing ability of NK cells can boost the immune system and enhance the effectiveness of monoclonal antibody-based therapies.

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