CORRELATION BETWEEN THE SENSITIVITY OR RESISTANCE TO IL-2 AND THE RESPONSE TO CYCLOPHOSPHAMIDE OF 4 TUMORS TRANSPLANTABLE IN THE SAME MURINE HOST

We have studied the anti-tumor response to cyclophosphamide (CTX) in DBA/2 mice transplanted s.c. with 4 tumors exhibiting different responses to IL-2: ESb lymphoma and Friend leukemia cells (non-responsive or poorly responsive, respectively), pII-R-Eb and Eb lymphoma cells (both highly responsive to IL-2). CTX injections on days 7, 14 and 21 resulted in a significant anti-tumor response in mice transplanted s.c. with Friend leukemia cells or ESb cells, whereas no anti-tumor effect was observed in mice injected with Eb or pII-R-Eb cells. All 4 tumor cell lines were equally sensitive to the cytotoxic effects of mafosfamide, an in vitro active analogue of CTX. To define the host mechanisms responsible for the lack of an anti-tumor effect of CTX in mice transplanted with IL-2-responsive tumors, we studied several aspects of the spontaneous or IL-2-induced anti-tumor response in mice transplanted with pII-R-Eb cells. Injection of monoclonal antibodies (MAbs) to IFN-gamma completely abolished the anti-tumor effects of IL-2. Using a Winn assay, clear-cut anti-tumor activity was found in spleen cells from mice transplanted with the IL-2-responsive tumors. This activity was abolished by CTX, which also abrogated the anti-tumor response to IL-2 in mice injected with pll-R-Eb cells. Our results indicate an inverse correlation between sensitivity to IL-2 and response to CTX and emphasize the importance of initial host-tumor interaction in determining the type of response to IL-2 or CTX. (C) 1995 Wiley-Liss, Inc.