Inhibitory effect of Propionibacterium acnes-activated macrophages on the tumor metastasis enhanced by tumor-specific immunosuppression.
The present study deals with the mechanism by which Propionibacterium acnes (P. acnes) prevents metastasis formation in C3H/He mice which had been rendered tolerant to tumor-associated transplantation antigen (TATA) of syngeneic X5563 plasmacytoma by intravenous (iv) inoculation of 10(6) X-irradiated tumor cells 3 times at 4-day intervals. In these TATA-tolerant mice, systemic metastasis formation was enhanced after intradermal (id) implantation of viable tumor cells, even if the tumor was resected surgically 7 days thereafter. Administration of P. acnes to these TATA-tolerance mice induced appreciable prevention of the metastasis formation. When we passively transferred P. acnes-activated peritoneal exudate cells (PECs) instead of P. acnes into TATA-tolerant mice, successful prevention to metastasis was also observed, irrespective of whether they were derived from TATA-tolerant mice or from normal naive mice. In both in vivo and in vitro assay systems, the P. acnes-activated PECs from TATA-tolerant mice as well as from normal naive mice showed potent anti-tumor activity. In the in vitro assay, anti-tumor effector cells in P. acnes-activated PECs were found to reside in a plastic adherent population resistant to treatment with anti-Thy-1 plus complement. These results are consistent with the view that effector cells for the prevention of metastasis are activated macrophages. The significance of these findings is discussed in relation to the possibility of the future application of an immunomodulator which activates macrophages to prevent metastasis.
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D005260:Female; D006649:Histocompatibility Antigens / Q000276:immunology; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology; D010537:Peritoneum / Q000166:cytology; D011425:Propionibacterium acnes / Q000276:immunology*
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens