Comparison of tumor-associated transplantation antigens of sublines of methylcholanthrene-induced murine tumors passaged separately in vivo for over a decade.

Two sublines of the methylcholanthrene-induced P815 mastocytoma, which had been passaged in vivo in separate institutions for over a decade, were compared for the expression of tumor-associated antigens in common. In cytotoxicity assays in vitro, the sublines were found to differ in expression of tumor-associated antigen(s) that were recognized by cytotoxic lymphocytes. However, in assays of tumor rejection in vivo, the sublines were found to express tumor-associated transplantation antigens in common. Both sublines were capable of inducing reciprocal cross-protection against the growth of a challenge implant of tumor cells of either subline, and both sublines were capable of inducing immunity that upon transfer of spleen cells from immunized mice to appropriate immunodeficient recipients would result in the complete regression of already established tumors of either subline. Similarly, two sublines of the methylcholanthrene-induced Meth-A fibrosarcoma that had been passaged separately in vivo for over a decade were also found to induce reciprocal cross-protection against a subsequent implant of cells of either subline. These results indicate that the expression of tumor-associated transplantation antigens by two methylcholanthrene-induced immunogenic tumors is quite stable and suggest that the generation of tumor-associated transplantation antigen variant cells occurs infrequently. Therefore, an explanation for the progressive growth of immunogenic tumors based on the emergence of nonimmunogenic variants is unlikely, and the probability that the emergence of antigenic variants will lead to the failure of specific adoptive immunotherapy is low. Furthermore, the results indicate that the specificity of the immune response of mice to tumors as defined by transplantation immunity in vivo and lymphocyte cytotoxicity in vitro may be quite different. Therefore, using antigenic differences defined by in vitro cytotoxicity assays to explain the behavior of immunogenic tumors in vivo should be done with caution.