Immunological mechanisms in metastatic spread and the antimetastatic effects of Corynebacterium parvum

Summary. The effects of the host's immune response on metastatic spread was investigated by observing the numbers of pulmonary metastases that developed from an s.c. implant of the Lewis lung carcinoma in C57BL mice in which different cell populations had been suppressed. Macrophage function was impaired by treatment with silica (Si), cortisone acetate (CA), or trypan blue (TB). T-cell function was depressed by adult thymectomy and sublethal irradiation, or by treat-ment with antilymphocyte serum (ALS). Metastasis was significantly increased and phagocytic activity decreased by Si and CA, but were unaffected by TB. Thymectomy and irradiation had no effect on metastases, whereas ALS when given before, but not after tumour growth, reduced their number. The antimetastatic action of the immunopotentiating agent C. parvum was investigated in these immunologically impaired mice. It was unaffected by Si, CA or TB. However, the inhibiting effect of these agents on phagocytic activity was overcome by treatment with C. parvum. Its antimetastatic action was unaffected in mice which had been thymectomized and irradiated, but could be abrogated by ALS. However, ALS was only able to prevent this activity if given before tumour growth; it was ineffective if given after tumour growth. This study showed that metastatic spread was inversely related to phagocytic activity. The antimetastatic effect of C. parvum appears to be mediated through macrophages in concert with a subpopulation of T lymphocytes, which were con-sidered to be necessary in the sensitization arm of the response as opposed to the effector arm of this response. ALTHOUGH successful treatment of patients with primary neoplasms is often possible, death frequently occurs from disseminated tumour. However, there is evidence from animal studies that the immunological response of the host deals more effectively with distant foci than with a single primary tumour (Milas et al., 1974) and immunotherapy may be more effective in this situation. Killed Corynebacteriurn parvum is a powerful immunopotentiating agent (Hal-pern et al., 1963; Biozzi et al., 1968