Tumor Selection In Vivo for Reduced Sensitivity to Natural Resistance and Natural Antibodies

Abstract

The contribution of natural antibodies (NAb) to the selective elimination of tumor variants in vivo was studied to further support the hypothesis that NAb participate in host-mediated natural resistance (NR) against neoplasia. Tumors obtained after the sc, ip, or iv inoculation of the natural killer cell-resistant, natural antibody-sensitive L5178Y-F9 tumor clone into syngeneic DBA/2 mice were tested for their sensitivity to NR in the [¹³¹l]5-iodo-2′-deoxyuridine elimination assay and to serum NAb in the presence of complement. Cells removed from the ip or sc sites of tumor inoculation exhibited a reduced susceptibility to syngeneic NR and to syngeneic but not to allogeneic NAb. Tumors recovered from the spleen, brain, and lungs after iv inoculation also expressed a decreased sensitivity to both syngeneic NR and NAb. These data suggest that NR against tumors is widely disseminated and support the hypothesis that NAb participate in this antitumor defense, including the control of metastatic spread of disease. Tumors previously selected in vivo also exhibited reduced sensitivity to complement-mediated lysis by NAb acquired in the peritoneum. The correlation observed between this sensitivity to complement and the recovery of tumor cells after the ip injection of L5178Y-F9 contribute to the evidence that NAb acts in vivo.