Antitumor Activity Of Macrophages Research Articles

Antitumor activity of macrophages induced by Corynebacterium liquefaciens.

Corynebacterium liquefaciens can induce a marked resistance to tumor cell (AH-7974) challenge in Donryu rats. This effect was also induced in T-cell-deficient athymic nude mice. The macrophages harvested from the peritoneal cavity of a rat injected with C. liquefaciens showed a marked inhibition of tumor growth in vitro. Therefore, the effector cells were assumed to be peritoneal macrophages. The time needed for activation of macrophages in vivo was within 3 to 5 days after injection of C. liquefaciens. Before or after this period, the peritoneal macrophages did not inhibit tumor cell proliferation. Furthermore, normal peritoneal macrophages were activated in vitro by C. liquefaciens and displayed remarkable antitumor activity. These results suggest that C. liquefaciens rendered the macrophages inhibitory to tumor cells even under T-cell depleted condition. On the other hand, in vitro antitumor activity of the activated macrophages disappeared completely after in vivo treatment of the peritoneal cavity of a rat with Trypan Blue, a lysosomal enzyme blocker. Resistance of the rat induced by C. liquefaciens to tumor cells was also abrogated by Trypan Blue treatment just 1 day before tumor cell inoculation. Trypan Blue blocked the acid-phosphatase (a marker enzyme of lysosomes) activity of the activated macrophages but it seemed not to affect other macrophage activities, at least in the following two points; normal macrophages treated with Trypan Blue had almost normal phogocytic function of India ink particles and, moreover, they could be rendered tumoricidal, same as normal macrophages, in vitro by C. liquefaciens.

Macrophage activation and anti-tumor activity of biologic and synthetic agents.

Systemic administration of the synthetic immunopotentiator pyran, was as effective as the use of the biologic immunopotentiator BCG in activating macrophages and in inhibiting the Lewis lung carcinoma and MCA 2182 sarcoma. Several other synthetic polyanions also activated macrophages and exhibited some anti-tumor activity, but none were as effective as pyran. Cell-wall fractions such as the Ribi vaccine and MER were considerably less effective than BCG. The anti-tumor activity of pyran against the virtually non-immunogenic Lewis lung carcinoma involved non-specifically activated macrophages, and both anti-tumor activity and macrophage activating ability persisted over a 100-fold range of drug from 0.5 mg/kg to 50 mg/kg. The ability of activated macrophages to destroy tumor cells was abrogated by treatment with trypan blue, an inhibitor of macrophage lysosomal enzymes. In addition, preincubation of tumor cells with activated peritoneal cells at effector-cell:target-cell ratios of 20:1 and 5:1 markedly decreased tumor incidence and mortality. Glycogen-stimulated or unstimulated peritoneal cells were completely inactive in inhibiting tumor growth in vivo or exhibiting cytotoxicity in vitro, demonstrating the requirement for activated macrophages selective for tumor-cell destruction.

Inhibition of tumor growth in vivo and in vitro by macrophages from rats treated with a streptococcal preparation, OK-432.

The role of macrophages from rats treated with a streptococcal preparation (OK-432) for inhibition of syngeneic tumor growth was examined both in vivo and in vitro. Treatment of rats with OK-432 intraperitoneally resulted in a transient inhibition of ascites tumor growth and concomitant increase in survival time. Peritoneal exudate cells from these rats completely suppressed tumor growth when admixed with tumor cells and transferred subcutaneously to syngeneic recipient rats. No such effect was observed with tumor cells from saline-treated control rats. The macrophages were responsible for the neutralization of tumor growth, since the removal of adherent cells from peritoneal exudate cells of rats treated with OK-432 resulted in the abrogation of their antitumor activity. To further investigate the antitumor activity of macrophages, an in vitro cytotoxicity assay was carried out on several tumor cell lines. A complete target cell destruction was brought about by macrophages from the rats treated with OK-432 but not from the control animals. The tumor cytotoxicity mediated by macrophages activated with OK-432 was regarded as non-specific because they could damage all the target cell lines tested.

In vivo cortisone sensitivity of nonspecific antitumor activity of Corynebacterium parvum-activated mouse peritoneal macrophages.

The nonspecific antitumor activity of Corynebacterium parvum-activated mouse peritoneal macrophages in vitro was inhibited by their prior treatment with cortisone acetate in vivo. Inhibition was marked (60 percent) 24 hours after cortisone injection and was still significant at 7 days, but antitumor activity was completely recovered by 9 days. This transient inhibition was sufficient to abolish the non-specific protection afforded by C. parvum in an in vivo pretreatment model.