Mechanism of immunologically specific killing of tumour cells by macrophages.

Abstract

THE increase in anti-microbial activity of macrophages which occurs in animals that have been infected with living microorganisms is frequently non-specific1. In contrast, the anti-tumour activity of macrophages from immunized animals has been demonstrated in vitro to be immunologically specific2,3. The experiments to be described may throw light on this paradox. They show that the killing of tumour cells by macrophages is made up of an immunologically specific interaction which is followed by a non-specific lethal reaction. A similar pattern has been described for the bactericidal action of immune macrophages3. We have described three ways of obtaining immunologically specific macrophages cytotoxic to tumour cells3,5. These are (1) from the peritoneal cavity of suitably immunized mice (see later); (2) “arming” in vitro by contact of non-immune macrophages with spleen cells from hyperimmunized mice, and (3) “arming” in vitro by exposure of non-immune macrophages to the cell-free supernatant obtained when spleen cells from immunized mice are cultured with the specific antigen. All such macrophages, on coming into contact with specific antigens, undergo a transformation (referred to as “activation”) which renders them capable of killing. The actual destruction of the target cell following direct contact with the “activated” macrophages is non-specific. Moreover, this non-specific killing may also be demonstrated by macrophages “armed” against tubercle bacilli (BCG) which are “activated” after exposure to the solubilized protein derivative from tubercli bacilli, PPD, and are able to kill tumour cells. In the original experiments3,5 in which target lymphoma cells were added to “armed” macrophages the immunologically specific stage and the non-specific stage of the cytotoxic reactions were not separated and occurred sequentially (Fig. 1).