Murine natural anti-tumor antibodies. II. The contribution of natural antibodies to tumor surveillance.

The objective of this study was to investigate whether natural anti-tumor antibodies (NAb) contributed to the surveillance of small inocula of syngeneic tumors. Experiments were designed to distinguish between NAb and NK-mediated host resistance. Four approaches were used: (1) the isolation of tumor variants differing in their tumorigenicity and susceptibility to these mechanisms, and to activated macrophages; (2) a comparison of the effects of adjuvants on the modification of both host resistance and the activity of these effectors; (3) the relationship between the ontogeny of the natural resistance mechanisms and tumorigenicity in aged mice; and (4) the use of a Winn-type assay. These studies provided support for a role in natural resistance correlated with both the ability of tumors to bind NAb, and the production of NAb in adjuvant-stimulated mice. Furthermore, the frequency of tumors observed after tumor challenge more closely correlated with the ontogeny of natural antibody than NK cells, and tumors coated with NAb were less tumorigenic than controls. The reduced tumorigenicity of an NK-sensitive tumor, when compared to an NK-resistant variant of the same line, provided evidence for NK-cell-mediated natural resistance in young adult mice. It was concluded that natural resistance to tumors is a complex phenomenon dependent on the tumor phenotype, as well as the activity of several effector mechanisms, and that natural anti-tumor antibody must be considered an important component of host resistance.