Ultrastructural studies of histiocyte-tumor cell interactions during tumor regression after intralesional injection of Mycobacterium bovis.

We made an ultrastructural study of the site of a transplanted syngeneic hepatocarcinoma and its draining lymph nodes in inbred guinea pigs, in the presence and absence of Mycobacterium bovis strain Bacillus Calmette-Guérin.The bacillus was injected into the growing intradermal tumor 7 days after transplantation, at which time it had metastasized to the first regional lymph node. Critical morphological similarities were found among activated histiocytes in the various reactive regions: infiltrating at the tumor site, autochthonous to the draining lymph node, migrating from the tumor site to the subcapsular marginal sinus of the draining lymph node, and infiltrating into the medullary sinuses of the lymph node. This observation indicates that these are all forms of a specific class of cell within the macrophage-histiocyte series. The cytopathic effect of these activated histiocytes on tumor cells is mediated by cell surface contact; we observed sizeable areas of fusion of the cellular membranes of histiocytes and hepatocarcinoma cells. Thus, destruction of target cells by nonphagocytic mechanisms may be a phenomenon related to activated but not specifically sensitized cells of the macrophage-histiocyte series.