serial killing of tumor cells by human natural killer cells – enhancement by therapeutic antibodies连续杀害人类自然杀伤细胞,增强肿瘤细胞的治疗性抗体.pdfVIP
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serial killing of tumor cells by human natural killer cells – enhancement by therapeutic antibodies连续杀害人类自然杀伤细胞,增强肿瘤细胞的治疗性抗体
Serial Killing of Tumor Cells by Human Natural Killer
Cells – Enhancement by Therapeutic Antibodies
Rauf Bhat, Carsten Watzl*
Institute for Immunology, University Heidelberg, Heidelberg, Germany
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.
Citation: Bhat R, Watzl C (2007) Serial Killing of Tumor Cells by Human Natural Killer Cells ?– Enhancement by Therapeutic Antibodies. PLoS ONE 2(3):
e326. doi:10.1371/journal.pone.0000326
INTRODUCTION
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