[Enhancement of antitumor immune responses by bleomycin]

We examined the therapeutic effect of antitumor antibiotic, bleomycin (BLM), using an experimental model of WKA rats and KMT-17 tumor. BLM (5 mg/kg/day) was administered ip for 5 days. The therapeutic effect of BLM was found to be dependent upon the timing of BLM-administration. A remarkable difference in therapeutic effect was observed when BLM was administered from the eighth day after tumor inoculation (late BLM-treatment) rather than when BLM was administered from the day following tumor inoculation (early BLM-treatment) (cured rats/treated rats: 10/21 and 2/16 respectively). By means of a Winn assay, enhancement of tumor neutralizing activity observed in spleen cells from rats given late BLM-treatment but not in spleen from rats given early BLM-treatment. The enhanced tumor neutralizing activity of spleen cells from rats given late BLM-treatment were suppressed by adding spleen cells from untreated tumor bearing rats. The antitumor transplantation resistance in rats immunized with irradiated KMT-17 cells was abrogated by an adoptive transfer of spleen cells from untreated tumor bearing rats or from rats given early BLM-treatment, but not by the spleen cells from rats given late BLM-treatment. These results suggest that BLM-administration during the late stage of tumor bearing eliminates immuno-suppressor cells and results in the enhancement of antitumor immune responses. The enhanced tumor neutralizing activity of spleen cells from rats given late BLM-treatment was mediated by both T-cell fraction and adherent macrophage fraction. The BLM treatment enhanced the in vitro cytolytic activity of splenic and peritoneal macrophages [( 125I] iododeoxyuridine release assay).(ABSTRACT TRUNCATED AT 250 WORDS)