Overcoming Suppression of Antitumor Immune Reactivity in Tumor-bearing Rats by Treatment with Bleomycin

Abstract

We investigated the immunological role of bleomycin (BLM) in the treatment of KMT-17 fibrosarcoma-bearing rats. We were able to detect antitumor immune reactivity by using a mixed-lymphocyte tumor culture in spleen cells shortly after the transplantation of a KMT-17 fibrosarcoma in syngeneic Wistar King Aptekman/HMK rats. The reactivity declined following the progression of the tumor and was completely inhibited 11 days after the tumor transplantation. After the 11th day, however, spleen cells from BLM-treated KMT-17-bearing rats demonstrated higher antitumor immune reactivity. This result corresponds to those we obtained from an in vivo tumor-neutralizing assay (Winn assay). Macrophages from untreated tumor bearers were unable to inhibit the immune reactivity against KMT-17 cells in the mixed-lymphocyte tumor culture. Neither the tumor-bearing state nor the BLM treatment seemed to have any significant influence on another macrophage function, the antigen-presenting cell activity. However, a T-enriched fraction from untreated KMT-17 bearers showed a definite suppression activity on the generation of cytotoxic T-lymphocyte activity against KMT-17 tumor in the mixed-lymphocyte tumor culture; in contrast, no T-suppressor activity could be detected in the same fraction taken from BLM-treated tumor bearers. Our investigation suggests that BLM eliminates the tumor-specific T-suppressor activity without having any influence on responder T-lymphocytes in the cell-mediated antitumor immune reactivity.