Adoptive immunization against an established tumor with cytolytic versus memory T cells. Immediate versus delayed onset of regression

Abstract

Intradermal injection of an admixture of P815 tumor cells and Corynebacterium parvum results in the emergence of a tumor that grows progressively for 9-10 days and then undergoes complete regression. Tumor regression is preceded by a cytolytic T cell response in the spleen that peaks on day 10 and then undergoes progressive decay until days 15-16 when cytolytic T cells can no longer be detected. Passive transfer of 10-day or 30-day spleen cells to T-cell-deficient recipients bearing a 4-day tumor resulted in complete tumor regression. However, whereas passively transferred 10 day spleen cells caused the onset of tumor regression within 2 days, passively transferred 30-day spleen cells did not cause tumor regression until after a 6-8-day delay. Again, the antitumor function of 10-day spleen cells could be eliminated by treatment with cyclophosphamide and vinblastine sulfate, whereas 30 day spleen cells were resistant to both agents. These results indicate that 10-day spleen cells are physiologically different from 30-day spleen cells. The results are consistent with the interpretation that passively transferred 10-day spleen cells cause rapid onset of tumor regression because they are cytolytic T cells and have an immediate capacity to destroy the tumor. In contrast, 30-day spleen cells are helper or memory T cells with no capacity at the time of transfer to destroy the tumor.