Immunity to MCA-induced rat sarcomas: analysis of in vivo and in vitro results

Three in vivo techniques were used to establish the specificity of tumor immunity induced after sensitization of F344 rats to syngeneic MCA-induced sarcomas: (1) post-excision resistance to tumor challenge, (2) passive tumor neutralization (the Winn test), and (3) concomitant immunity. In general, these assays revealed unique non-cross-reactive antigens associated with each of three sarcomas, FMF1, FMM2, and FMM3. However, spleen cells from tumor-sensitized rats did not demonstrate cell-mediated cytotoxicity in vitro corresponding to the specificity of tumor resistance in vivo. In the (3H)-proline cytotoxicity assay, spleen cells from FMM3 tumor-bearing rats or from FMM3 tumor-immune rats were not selectively cytotoxic for cultured FMM3 target cells. Parallel analysis of spleen cells from normal or FMM3-sensitized rats using the Winn assay and the (3H)-proline assay revealed that (1) spleen cell cytotoxicity in vitro did not correlate with effective tumor protection in vivo; and (2) normal spleen cells were cytotoxic against cultured sarcoma target cells in vitro and inhibited tumor growth in vivo. Thus, passive tumor protection by normal spleen cells in vivo corresponded with the demonstration of natural cytotoxicity in vitro, but induced specific anti-tumor reactivity was observed only in vivo.