Role of respiratory-burst products from polymorphonuclear leukocytes in the antitumor activity of Propionibacterium acnes vaccine

Abstract

Tumor cells injected into Balb/c mice together with heat-killed 48-h P. acnes cells were rendered nontumorigenic as early as 12 h after injection, as determined by the inability of the tumor cells to give rise to tumors when transferred to a new host. Determination of tumor cell antigen levels by ELISA indicated that the tumor antigens had virtually disappeared by 24 h after injection of tumor cells and P. acnes. In contrast, in control animals injected with tumor cells only, there was an initial drop in tumor antigen levels at 12 h, after which the level rose steadily and tumors developed in 7–10 days. Since the cellular exudate at 12 h was almost entirely composed of polymorphonuclear leukocytes (PMN), we tested the ability of PMN, stimulated by phagocytosis of 48-h P. acnes cells, to produce substances toxic to tumor cells. Results indicated that the supernatant fluid from a phagocytosis mixture of PMN and P. acnes contained material toxic to tumor cells and also to Chinese hamster ovary cells. Tests with scavengers and inhibitors of oxygen-derived radicals suggested that the toxic material is either hydrogen peroxide (H₂O₂) or hydroxyl radicals (OH). Suspensions of 12-h P. acnes, P. acnes cells walls, P. freudenrichii, or latex beads were ineffective in preventing tumor growth, and induced little toxicity when phagocytosed. We conclude that in this test system 48-h P. acnes prevents tumor growth by stimulating the production of toxic oxygen metabolites during phagocytosis by PMN.