In Vivo Inhibition of Antitumor Immunity by Embryonic Antigens

Abstract

Adult female BALB/c mice were immunized against the 3-methylcholanthrene–induced fibrosarcoma ST2 by growth and excision, and then injected with either neoplastic or embryonic mitomycin-C-blocked syngeneic cells before receiving a subcutaneous challenge of 10⁵ ST2 cells. Other groups of similarly immunized females were intraperitoneally implanted with cell-impermeable diffusion chambers containing neoplastic or embryonic tissues, or mated to syngeneic males, before being challenged with ST2 cells. The mice immunized and injected with blocked ST2 but not with embryonic or antigenically unrelated neoplastic cells showed a resistance to the growth of ST2 significantly lower than that of immune mice given normal adult cells. This was particularly evident when ST2 blocked cells were given parenterally but was also detectable when ST2 blocked cells were cultured within diffusion chambers kept in tumor–excised mice. The syngeneic pregnancy had no effect on the antitumor immunity. In a subsequent study, BALB/c females were challenged with the same number of ST2 tumor cells as above, but the challenge was performed at days +4, +2, 0, –-2, –-4 from excision, and the blocked neoplastic embryonic or normal adult cells were given starting at the day of challenge. It was found that when the challenge was done 4 and 2 days after the excision, the administration of either antigenically-related tumor cells or embryonic cells could reduce the antitumor immune protection, while no such an effect was detectable in the other experimental groups. Thus, in addition to tumor-associated transplantation antigens, embryonic antigens also seem to be able to impair the developing antitumor immunity provided they are given within four days from the excision of the immunizing growth.