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Lack of Correlation between Natural Killer Activity and Tumor Growth Control in Nude Mice with Different Immune Defects

Laboratory of Experimental Therapeutics and Metabolism, Developmental Therapeutics Program, Division of Cancer Treatment [Ø. F., C. N. S., G. R. L., M. R. B.] and Veterinary Resources Branch, Division of Research Services [C. T. H.], NIH, Bethesda, Maryland 20205, and Department of Immunology, Litton Bionetics, Inc. [G. B. C.], Kensington, Maryland 20814

To elucidate the in vivo role of natural killer (NK) cells, the growth of several murine and human tumors was studied in four variants of athymic, nude mice with different levels of NK activity.

Beige-nude mice, homozygous for both the beige and the nude genes, had very low levels of NK activity, and their response to the B-cell mitogen, bacterial lipopolysaccharide, was lower than that of high-NK, adult NIH nude mice. Young and adult NIH nudes had different NK levels and showed different response in assays for K-cell, T-cell, and B-cell activity. The B-cell-defective NIH-II mice had slightly lower NK levels than adult NIH animals, but much lower response in the antibody-dependent cell-mediated cytotoxicity assay.

No correlation was found between host NK activity and the s.c. growth of various human (LOX, CEM, K562) and murine (YAC-1) tumor cells. Low NK activity was not associated with increased lung colony formation in a metastasis model using i.v.-injected human (LOX) and murine (B16F10) melanoma cells. No relationship was found between host NK activity and the rate of elimination of i.v.-injected 5-iodo-2'-deoxyuridine-labeled LOX, B16F10, and YAC-1 cells from lungs, liver, or spleen.

The results fail to support the view that NK cells exert significant direct effects on tumor cells in vivo.

¹ To whom requests for reprints should be addressed, at Norsk Hydros Institute for Cancer Research, The Norwegian Cancer Society and The Norwegian Radium Hospital, Montebello 0310 Oslo 3, Norway.

Received 2/17/84. Accepted 6/ 1/84.

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