Antitumor and immunologic effects of a pyridine-extracted fraction of Propionibacterium acnes.

The antitumor and immunological effects of a pyridine extractable fraction of Propionibacterium acnes were tested in a murine ovarian teratocarcinoma (MOT) model. Previous studies have demonstrated that tumor rejection in this model depends upon sequential activation of tumoricidal neutrophils (PMNs) followed by cytostatic macrophages. The pyridine extract significantly prolonged the survival of mice challenged with 10(3) or 10(4) MOT cells but had little impact on a 10(5) tumor inoculum. In vivo cytoreduction occurred within the first 24 h following IP treatment which correlated temporally with the influx of tumoricidal PMNs into the peritoneal cavity. Immunotherapy failure in mice challenged with 10(5) MOT cells occurred between 48 and 72 h after treatment when macrophage chemotaxis into the peritoneal cavity was initiated. Although injection of unfractionated bacteria activated MOT-cytostatic macrophages, the pyridine extract was deficient in this regard. Intraperitoneal injection of the pyridine extract resulted in an early (day +1) depression and late (day +5) enhancement of peritoneal NK cytotoxicity. These data suggest that the retention of neutrophil-activating moieties in the pyridine extract are sufficient for antitumor effects against low tumor inocula while the depletion of macrophage-activating determinants results in diminished effects against larger tumor cell challenges.