Nature 292, 848 - 850 (27 August 1981); doi:10.1038/292848a0

Natural killer cells kill tumour cells at a given stage of differentiation

Magnus Gidlund, Anders Örn, Paul K. Pattengale^*, Mats Jansson^†, Hans Wigzell & Kenneth Nilsson^‡

Department of Immunology, University of Uppsala Biomedical Centre, Box 582, S-751 23 Uppsala, Sweden
^*Department of Pathology, University of Southern California, School of Medicine, Los Angeles, California 90033, USA
^†Department of Microbiology, University of Uppsala Biomedical Centre, Box 581, S-751 23 Uppsala, Sweden
^‡Wallenberg Laboratory, Box 562, S-751 22 Uppsala, Sweden

Natural killer (NK) cells have unique surface features and physiological characteristics and a selective ability to lyse some, but not other, target cells^1,2. However, the basis of this selectivity remains obscure at both effector and target cell levels. Proposed specific NK-cell target moieties³⁻⁵ include glycolipids, and glycoproteins unrelated to the major histocompatibility complex, while malignant and certain normal cells have been found to be susceptible to NK-cell-mediated cytolysis⁶⁻⁸. There is good evidence that NK cells can inhibit the outgrowth of small numbers of transplanted tumour cells in vivo ^9,10 and can restrict the establishment of secondary metastasis^11,12. It has thus been speculated that NK cells function as a primitive, thymus-independent immune system using phylogenetically preserved target structures to form a cell-mediated resistance barrier against the outgrowth of certain tumour cells¹. The presence in the thymuses of neonatal mice and humans^8,13 and in the marrow of human fetuses, of apparently normal cells which are quite sensitive to NK cells suggested that NK cells might have an increased ability to cause the lysis of cells at a particular stage of their differentiation. In agreement with this concept, embryonal carcinoma cells at various stages of differentiation display a strikingly different susceptibility to NK-cell-induced lysis¹⁴. Here only cell types representing early stages were sensitive to NK-cell-mediated cytolysis, whereas the more differentiated endodermal cell lines showed close to complete resistance. The above data would thus support the view that, in vivo, depending on the stage of differentiation, both normal and malignant cells are under surveillance by NK cells. Here we have considered the question of differentiation-related NK-cell susceptibility using defined cell lines known to undergo controlled differentiation in the presence of various agents. Three tumour cell-lines were investigated, and all demonstrated a striking positive correlation between a decrease in NK-cell susceptibility and the induction of differentiation by the various inducers. Our findings support the view that susceptibility to NK-cell mediated lysis may vary according to the stage of differentiation of the target cell.

References

1.	Kiessling, R. & Wigzell, H. Immun. Rev. 44, 165−208 (1979). | PubMed | ISI | ChemPort |
2.	Herberman, R. B. (ed.) Natural Cell-Mediated Immunity Against Tumours (Academic, New York, 1980).
3.	Roder, J. C. Ährlund-Richter, L. & Jondal, M. J. exp. Med. 150, 471−480 (1979). | Article | PubMed | ISI | ChemPort |
4.	Young, W. W., Durdik, J. M., Urdal, D., Hakomori, S.-I. & Henney, C. S. J. Immun. 126, (1981). | PubMed | ChemPort |
5.	Kiessling, R. & Wigzell, H. Curr. Topics Microbiol. Immun. (in the press).
6.	Kiessling, R., Klein, E. & Wigzell, H. Eur. J. Immun. 5, 112−117 (1975). | ISI | ChemPort |
7.	Cudkowicz, G. & Hochman, P. S. Immun. Rev. 44, 13−41 (1979). | PubMed | ISI | ChemPort |
8.	Hansson, M., Kiessling, R., Andersson, B., Kärre & Roder, J. Nature 278, 174−176 (1979). | PubMed | ISI | ChemPort |
9.	Haller, O., Hansson, M., Kiessling, R. & Wigzell, H. Nature 270, 609−611 (1977). | PubMed | ISI | ChemPort |
10.	Riesenfeldt, I. et al. Int. J. Cancer 25, 399−403 (1980). | PubMed | ISI | ChemPort |
11.	Talmadge, J., Meyers, K., Prieur, D. & Starkey, J. Nature 284, 622−624 (1980). | PubMed | ISI | ChemPort |
12.	Hanna, N. & Fiddler, I. J. natn. Cancer Inst. (in the press).
13.	Hansson, M. & Kiessling, R. in NK Cells: Fundamental Aspects and Role in Cancer (ed. Herberman, R. B.) (North-Holland, Amsterdam, in the press).
14.	Stern, P., Gidlund, M., Örn, A. & Wigzell, H. Nature 285, 341−342 (1980). | PubMed | ISI | ChemPort |
15.	Andersson, L. C., Jokinen, M. & Gahmberg, C. G. Nature 278, 364−365 (1979). | PubMed | ISI | ChemPort |
16.	Pattengale, P. K. et al. Int. J. Cancer (in the press).
17.	Sundström, C. & Nilsson, K. Int. J. Cancer 17, 565−577 (1976). | PubMed | ISI | ChemPort |
18.	Nilsson, K. et al. Mod. Trends Hum. Leukaemia 26 (in the press).
19.	Koren, H. S., Andersson, S. J. & Larrick, J. W. Nature 279, 328−331 (1979). | PubMed | ISI | ChemPort |
20.	Nilsson, K., Andersson, L. C., Gahmberg, C. G. & Forsbeck, K. in New Trends in Human Immunology and Cancer Immunotherapy (eds Serrou, B. & Rosenfeld, C.) 271−282 (Doin, Paris, 1981).
21.	Gazitt, Y., Reuben, R., Deitch, A., Marks, P. & Ritkind, R. Cancer Res. 38, 3779−3785 (1978). | PubMed | ISI | ChemPort |
22.	Persson, H., Jansson, M. & Philipson, L. J. molec. Biol. 136, 375−394 (1980). | PubMed | ISI | ChemPort |
23.	Nilsson, K., Evrin, P. E. & Welsh, K. I. Transplantn Rev. 21, 53−84 (1974). | ChemPort |
24.	Blazar, B., Patarroyo, M., Klein, E. & Klein, G. J. exp. Med. 151, 614−627 (1980). | Article | PubMed | ISI | ChemPort |