[Ultrastructural characteristics of the regression of a Novikoff hepatoma transplanted into immunized rats].

In order to elucidate ultrastructure of tumoral rejection, we have studied the sequential morphological modifications of Novikoff hepatoma transplanted in striated muscle of normal and immunized rats. Specific immunity was induced by the repeated injection of small doses of tumor cells. One month after immunization, a tumorigenous dose was then injected in striated muscle. The animals were sacrificed at 1, 4, 6 or 7 and 14 or 21 days, and tissue samples of the zone of implantation were taken for morphological study. The transplanted tumor regressed in all immunized rats and the sequential ultrastructural examination of these tumors indicated three major phases in their regression: an initial phase (day 1) during which there was an inflammatory infiltrate rich in neutrophils, a reduction of the mitotic activity of tumoral cells and the necrosis of some of them; an intermediary phase (days 4-7) during which the intratumoral infiltrate was composed mainly of lymphocytes and macrophages. These cells surrounded the tumoral cells and eventually formed microgranulomas. Tumoral cells showed cytostasis and/or cytolysis; a final phase (days 14-21) where the tumor had completely disappeared and had been replaced by fibrous tissue and vacuolated macrophages. The morphologic aspect of the intermediary phase is characteristic of a regressive tumor. Our sequential observations clearly showed the sequestration of tumor cells by macrophages and suggest the contact cytolysis of tumor cells. The sequestration of target cells by macrophages might facilitate the concentration of the cytolytic substances in the area of intercellular contacts, and likewise protect these substances from neutralization by serum or tissue inhibitory factors.