NK CELLS FROM MAMMARY-TUMOR BEARING MICE DO NOT EXERT NATURAL-KILLER ACTIVITY BUT FUNCTION AS ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY EFFECTORS

We have previously found that natural killer (NK) activity is profound ly decreased in BALB/c mice bearing large mammary tumors. Kinetic stud ies showed that after 14 days of tumor implantation a reduction of 25- 40% of NK cytotoxicity can be observed and by 21 days only very low le vels of NK reactivity can be detected in the spleens of tumor bearers. Phenotypic analyses of the splenic NK cells of tumor bearing mice rev ealed that they have similar density, granularity and comparable level s of NK 2.1 antigen on their surfaces as compared to NK cells from nor mal mice. However, in tumor bearers there was a shift from a high surf ace asialo GM1-bearing NK population to low-density surface asialo GM1 -positive bearing cells. Phenotypically characterized NK cells were qu antitated to test the possibility that splenic NK cells from tumor bea rers migrated to other organs and were therefore at lower levels in th e spleen. No significant differences were observed in the percentages of NK cells from spleens from normal and tumor bearing mice. Using sin gle cell conjugate assays it was found that there was no impairment in the capacity of NK from tumor bearers to bind the NK-sensitive Yac-I cells, however, this event did not result in lysis of the target cells . To elucidate whether the lytic machinery of the tumor bearers' NK ce lls was inactivated, their capacity to effect antibody dependent cellu lar cytotoxicity (ADCC) was evaluated. In contrast to the results obse rved when NK activity was evaluated, NK cells from tumor bearing mice exerted higher levels of ADCC than their normal counterparts and they had a higher expression of Fc receptors on their surfaces. These resul ts suggest that the depression of NK activity observed in tumor bearin g mice occurs at a triggering step that is not necessary for the activ ation of the NK effectors via the Fc receptor and that no major impair ment of the lytic machinery occurs during mammary tumorigenesis.