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Immunology

In vivo eradication of MLL/ENL leukemia cells by NK cells in the absence of adaptive immunity

Abstract

It remains unclear how the immune system affects leukemia development. To clarify the significance of the presence of immune systems in leukemia development, we transferred MLL/ENL leukemia cells into immune-competent or immune-deficient mice without any preconditioning including irradiation. The wild-type mice did not develop leukemia, whereas all the Rag2−/−γc−/− mice lacking both adaptive immune cells and natural killer (NK) cells developed leukemia, indicating that leukemia cells were immunologically rejected. Interestingly, leukemia cells were also rejected in 60% of the Rag2−/− mice that lacked adaptive immune cells but possessed NK cells, suggesting that NK cells play a substantial role in the rejection of leukemia. Moreover, engraftment of leukemia cells was enhanced by NK cell depletion in Rag2−/− recipients and inhibited by transfer of NK cells into Rag2−/−γc−/− recipients. Upregulation of NKG2D (NK group 2, member D) ligands in MLL/ENL leukemia cells caused elimination of leukemia cells by NK cells. Finally, we found that leukemia cells resistant to elimination by NK cells had been selected during leukemia development in Rag2−/− recipients. These results demonstrate that NK cells can eradicate MLL/ENL leukemia cells in vivo in the absence of adaptive immunity, thus suggesting that NK cells can play a potent role in immunosurveillance against leukemia.

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Acknowledgements

We thanks Irving L Weissman (Stanford University) for kind gifts of Rag2−/−γc−/− mice, Michael L Cleary (Stanford University) for kind gift of MLL/ENL cDNA, Toshio Kitamura (Tokyo University) for kind gift of Plat-E cells, Hisashi Arase (Osaka University) for fruitful discussion and Ruriko Inoue (Osaka University) for technical assistance.

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Nakata, J., Nakano, K., Okumura, A. et al. In vivo eradication of MLL/ENL leukemia cells by NK cells in the absence of adaptive immunity. Leukemia 28, 1316–1325 (2014). https://doi.org/10.1038/leu.2013.374

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