Antitumor and immunologic effects of a pyridine-extracted fraction of Propionibacterium acnes
Abstract:
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.
Insights
A Propionibacterium acnes pyridine extract showed antitumor effects in a murine ovarian teratocarcinoma model by activating neutrophils. However, its efficacy decreased with higher tumor cell numbers due to reduced macrophage activation.
Area of Science:
- Immunology
- Microbiology
- Oncology
Background:
- Tumor rejection in the murine ovarian teratocarcinoma (MOT) model relies on sequential activation of tumoricidal neutrophils (PMNs) and cytostatic macrophages.
- Propionibacterium acnes is known to modulate immune responses.
Purpose of the Study:
- To evaluate the antitumor and immunological effects of a pyridine extractable fraction of Propionibacterium acnes in a murine ovarian teratocarcinoma (MOT) model.
- To investigate the role of neutrophils and macrophages in the observed antitumor activity.
Main Methods:
- Testing a pyridine extractable fraction of Propionibacterium acnes in a murine ovarian teratocarcinoma (MOT) model.
- Challenging mice with varying inocula (10(3), 10(4), 10(5)) of MOT cells.
- Assessing survival rates, in vivo cytoreduction, and immune cell infiltration (PMNs, macrophages).
- Evaluating Natural Killer (NK) cell cytotoxicity.
Main Results:
- The pyridine extract significantly prolonged survival in mice challenged with 10(3) or 10(4) MOT cells, but not with 10(5) cells.
- In vivo cytoreduction within 24 hours correlated with PMN influx.
- Immunotherapy failure occurred when macrophage chemotaxis was initiated (48-72 hours) for higher tumor loads.
- The extract enhanced NK cytotoxicity on day 5 but depressed it on day 1.
- The extract retained neutrophil-activating moieties but lacked macrophage-activating determinants.
Conclusions:
- The pyridine extract of Propionibacterium acnes demonstrates antitumor activity mediated by neutrophils against low tumor burdens.
- The depletion of macrophage-activating components in the extract limits its efficacy against larger tumor inocula.
- The findings highlight the differential roles of neutrophils and macrophages in this model and the extract's immunomodulatory properties.
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