Resistance of tumor-bearing mice to a second tumor challenge.

Antitumor resistance of mice bearing 3LL, M109, or Meth A tumors to a second tumor challenge was studied. The degree of inhibition of a second tumor growth in the tumor-bearing mice was a function of both the size of the primary tumor mass and the number of reinoculated tumor cells. Antitumor resistance of tumor-bearing mice is tumor nonspe cific and is observed only in the presence of the growing first tumor. Following removal of 3LL tumor, the resistance to the second challenge with 3LL or T-10 tumor cells completely disappeared. Antitumor resistance of tumor-bearing mice does not appear to be mediated by T-cells, natural killer cells, or macrophages, since similar results were observed in immunologically com petent and nude mice as well as in beige mice and in mice with functions of macrophages and natural killer cells suppressed by silica treatment. Growth inhibition of the reimplanted tumor cells does not appear to be a result of their elimination. Radiolabeled M109 tumor cells survived to the same degree at the local site of inoculation in tumor-bearing and non-tumor-bear ing control mice. The number of surviving radiolabeled tumor cells inoculated into the footpad of ¡mmunocompetentand nude mice was similar and did not depend on the presence or absence of growing first tumor. Despite the similarity in the survival of reinoculated tumor cells, their growth was inhibited only in the tumor-bearing mice. In mice bearing ¡mmunogenic Meth A tumors of different sizes (1 to 3 cm), the clearance of the reinoculated Meth A cells was significantly higher than in non-tumor-bearing mice. The number of surviving tumor cells was similar in mice bearing small (<1 cm) or large (>3 cm) tumors. However, complete prevention of the second tumor growth was observed in mice bearing huge tumor mass (^3 cm in diameter). These data may indicate that resistance of mice bearing immunogenic and nonimmunogenic tumors is mediated by different mechanisms. The resistance to a second tumor challenge in mice bearing nonimmunogenic tumor is due mainly to nonimmunological mechanisms. In contrast, the antitumor resistance in mice bearing immunogenic tumor is a function of antitumor immune reactions, although additional effects of nonimmunological mechanisms were also observed.