Quantitative studies of natural immunity to solid tumours in rats. NK activity in animals with primary or transplanted spontaneous tumours.

Abstract

Natural killer (NK) cell activity was measured in a quantitative 6 h chromium release assay using sarcoma MC7 cells as targets. The total NK lytic activity present in the spleen and blood of tumour-bearing animals was compared with the corresponding values for age/sex/parity-matched animals. Rats with primary spontaneous tumours in the breast or subcutaneous sites showed normal levels of NK activity, while rats with primary spontaneous kidney tumours had elevated NK activity, the degree of augmentation being greater with increasing tumour size. A similar elevation of NK activity was generally found in animals with large, transplanted, spontaneous or chemically-induced tumours. This augmentation could only detected when total lytic activity was considered: when NK activity was measured merely on a cell-for-cell basis, it often appeared to be depressed in such animals, in agreement with previous reports. However, with one rapidly metastasizing spontaneous tumour, a real depression of both spleen and blood NK activity was found. Small inocula of cells from non-immunogenic spontaneous mammary tumours or from other non-immunogenic spontaneous tumours caused no early increase in systemic NK activity when injected into the mammary pad, a site where spontaneous tumours frequently arise. However, cells from one immunogenic spontaneous tumour and 2/3 immunogenic chemically-induced tumours did occasionally stimulate significant early increases in NK activity when placed at this site. Early changes in peritoneal exudate NK activity were also investigated using small inocula of these tumours injected intraperitoneally. Augmentation of NK activity occurred with a 3-fold greater frequency following inoculation with immunogenic tumour cells than with non-immunogenic cells in this system. It can be concluded from these studies that: (1) spontaneous tumours do not selectively arise in members of an inbred strain with subnormal NK activity; (2) most large tumours in rats stimulate rather than depress NK activity; (3) early boosting of NK activity by small inocula of tumour cells placed in the mammary pad does not occur with non-immunogenic spontaneous tumours; (4) early boosting of NK activity in the peritoneal site does occur with non-immunogenic tumours, but with a very low frequency. The latter findings suggest that developing spontaneous tumours are unlikely to stimulate the NK system, and emphasize the importance of using syngeneic, spontaneous tumours for studying tumour-host relationships in animals.